Impact of Nicotine Exposure and withdrawal on Plasma glucose, insulin and glycated haemoglobin in high-fat diet fed wistar rats

Impact of Nicotine Exposure and withdrawal on Plasma glucose, insulin and glycated haemoglobin in high-fat diet fed wistar rats | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Impact of Nicotine Exposure and withdrawal on Plasma glucose, insulin and glycated haemoglobin in high-fat diet fed wistar rats Onyebuchi Obia, Ledu Nda-ue, Sunday Ogbu Ojeka, Azubuike Ogba, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3917916/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 18 Apr, 2024 Read the published version in East African Scholars Journal of Medical Sciences → Version 1 posted You are reading this latest preprint version Abstract Background to the study : Nicotine, which is the most abundant constituent of tobacco cigarette is one of the most commonly abused drugs. The duo of obesity and tobacco smoking increases the risk of cardiometabolic disorders. Methodology : The experiment involved 48 male wistar rats separated into 4 groups of 8 rats each. All the animals were placed on high-fat diet (Margarine; blue band) in addition to the different doses of nicotine in the experimental groups. Group 1 served as control and received distilled water, Groups 2, 3 and 4 received 200µg/kg, 400µg/kg and 800µg/kg of nicotine oral solution respectively. The experimental groups were placed on their respective doses of nicotine solution for an initial four weeks. Thereafter, four animals in each group were sacrificed and blood samples collected to determine their nicotine exposure plasma levels of glucose, insulin and glycated hemoglobin. The remaining four animals in each group continued without nicotine for another four weeks after which they were sacrificed and blood samples collected to determine their nicotine withdrawal plasma levels of glucose, insulin and glycated hemoglobin. Results : The results showed that exposure to the three concentrations of nicotine (200, 400 and 800µg/kg respectively) significantly caused a rise in plasma insulin levels but dose-dependent reduction in both glucose and glycated haemoglobin compared to their control groups. Four weeks after withdrawal of initial 200µg/kg nicotine there were no significant changes in the levels of plasma glucose, insulin and glycated haemoglobin compared to the nicotine exposed groups. Withdrawal, after initial exposure to 400µg/kg of nicotine was associated with significant rise in both the plasma glucose and glycated haemoglobin but no significant change in insulin compared to their respective nicotine exposed groups. Cessation, after initial exposure 800µg/kg of nicotine resulted in significant rise in plasma levels of glucose, glycated haemoglobin and insulin compared to their nicotine exposed groups. Conclusion : The possible reduction in food consumption and increased physical activity together with the increased levels of insulin in the plasma could contribute to the lowered plasma glucose shown in this study. The reduction in the levels of glycated haemoglobin following exposure to nicotine may be potentially beneficial in diabetic management. Therefore, reversal of plasma glucose and glycated haemoglobin levels could be achieved four weeks after cessation of 800µg/kg of nicotine. This result could suggest a possible association of nicotine cessation with decreased insulin sensitivity. Nicotine Plasma glucose insulin glycated haemoglobin high-fat diet Figures Figure 1 Figure 2 Figure 3 INTRODUCTION The global prevalence of cigarette smoking has remained unabated over the years ( 1 ) despite all the campaigns staged against it. Studies have associated higher risk of cardiovascular disorders and other conditions with cigarette smoking ( 2 ). Although some studies suggest that combining exercise or dietary factors could mitigate the risk of disease in cigarette smokers ( 3 , 4 ), it has remained a leading cause of preventable death globally ( 5 ). The most abundant constituent of tobacco cigarette is nicotine which has proven addictive effect on smokers, making it one of the most commonly abused drugs ( 6 , 7 ). Nicotine binds to nicotinic cholinergic receptors to stimulate the release of dopamine and thus adrenaline ( 8 , 9 ). The drug has significant effects on attention and memory ( 10 , 11 ). However, sudden withdrawal of nicotine has been associated with reversible impairment of attention and memory ( 12 ). Obesity, a global epidemic and major public health concern is basically characterized by excessive body fat accumulation. Comparatively, the prevalence of obesity amongst smokers is lower than that of non-smokers ( 13 ). Although, obesity alone is associated with increased risk of cardio-metabolic disorders. However, obesity paired with tobacco smoking further increases the risk of cardio-metabolic disorders and represent the largest challenges to public health ( 14 , 15 ). The causal correlation between nicotine and obesity is poorly understood, thus necessitating this study. Eating and smoking are behavioural traits that are to an extent controlled by the same reward mechanism ( 16 ). Studies have shown that nicotine may interfere with glucose-regulating mechanisms of the body ( 17 ). Withdrawal of nicotine as in quitting of cigarette smoking can result in intense cravings for nicotine, irritability, depression, insomnia, hunger, and difficulty concentrating ( 18 ). The increased appetite associated with nicotine withdrawal could be due to reactivation of pathways that were previously blocked by nicotine ( 19 ). Studies suggest that the nicotine withdrawal symptoms could result from the brain having no opposing force (dopamine) to dampen its effects. It is the lack of this opposing force that causes withdrawal symptoms ( 20 ). The aim of the present study was to investigate the effects of nicotine exposure and discontinuation on serum insulin, glucose and glycated haemoglobin of high-fat diet fed wistar rats. MATERIALS AND METHODS This study was carried out in the department of Human Physiology, Faculty of Basic Medical Sciences, University of Port Harcourt with ethical approval number: UPH/CEREMAD/REC/MM68/053. The experiment involved 48 male wistar rats separated into 4 groups of 8 rats each which were acclimatized for a period of two weeks being provided with standard animal chow and water ad libitum . After acclimatization, all the animals were placed on high-fat diet (Margarine; blue band) in addition to the different doses of nicotine in the experimental groups. Group 1 served as control and received distilled water, Groups 2, 3 and 4 received 200µg/kg, 400µg/kg and 800µg/kg of nicotine oral solution respectively. The experiment was performed in two phases. In the first phase, the experimental groups were placed on their respective doses of nicotine solution for 4 weeks. Thereafter, 4 animals in each group were sacrificed and blood samples collected to determine their nicotine exposure plasma levels of glucose, insulin and glycated hemoglobin. In the second phase of the experiment, nicotine was discontinued in the experimental groups. The remaining 4 animals in each group continued without nicotine for another four weeks after which they were sacrificed and blood samples collected to determine their nicotine withdrawal plasma levels of glucose, insulin and glycated hemoglobin. All the parameters were determined using standard methods and values recorded. Data were analyzed using SPSS vs 23 and presented in Tables and graphs. Continuous variables were expressed as mean ± SEM. The differences between each group were analyzed using paired sample t-test and ANOVA. Values of p < 0.05 were considered significant with a confidence level of 95%. RESULTS AND DISCUSSION Table 1 Effect of nicotine exposure on plasma glucose, insulin, and glycated hemoglobin of wistar rats Groups Glucose (mmol/l) Insulin (IU/l) HbA1 c (%) Control 7.78 ± 0.14 10.70 ± 0.77 6.50 ± 0.08 200µg/kg of nct 6.63 ± 0.49* 14.90 ± 1.07* 5.75 ± 0.32* 400µg/kg nct 5.35 ± 0.34* 18.88 ± 0.28* 4.95 ± 0.22* 800µg/kg of nct 4.73 ± 0.19* 15.88 ± 0.45* 4.55 ± 0.13* Values are mean ± standard error of mean *Significant compared to control. nct; nicotine. There was dose-dependent reduction in plasma glucose and glycosylated hemoglobin levels following exposure to nicotine. Whereas the plasma insulin levels increased significantly compared to control in high-fat diet fed wistar rats. Table 2 Withdrawal effects of nicotine on plasma glucose, insulin and glycated hemoglobin. Groups Glucose (mmol/l) Insulin (IU/l) HbA1 c (%) Control 6.95 ± 0.18 16.30 ± 0.35 5.98 ± 0.11 200µg/kg of nct 5.68 ± 0.41* 17.80 ± 2.46 5.18 ± 0.26* 400µg/kg nct 6.90 ± 0.11 21.15 ± 1.57* 6.20 ± 0.24 800µg/kg of nct 7.35 ± 0.27 22.75 ± 0.93* 6.28 ± 0.17 Values are mean ± standard error of mean *Significant compared to control. nct; nicotine. There was significant reduction in plasma glucose and glycosylated hemoglobin with the lowest dose of nicotine following withdrawal but no significant effect with the higher doses. Whereas the plasma insulin levels increased significantly with the higher doses following nicotine withdrawal in high-fat diet fed wistar rats. DISCUSSION Nicotine which is commonly used as a recreational drug is known to possess highly addictive properties. The present study examined the effect of nicotine exposure on the glycemia of high fat-diet fed wistar rats. The results showed that exposure to the three concentrations of nicotine (200, 400 and 800µg/kg respectively) significantly caused a rise in plasma insulin levels but reduction in both plasma glucose and glycated haemoglobin levels compared to their control group. Physiologically, insulin is known to drive glucose into the cells and therefore has an inverse relationship with plasma glucose ( 21 ). The reduction in both the plasma glucose and glycated haemoglobin were in a dose-dependent fashion. Previous studies have linked continues exposure to nicotine with increases in basal metabolic rate, thermogenesis and physical activity but reduction in food intake ( 22 , 23 , 24 ). Most of the stimulants of the central nervous system are often used as ergogenic aids ( 25 ) which increases energy utilization in endurance exercises. However, studies suggest that nicotine as a CNS stimulant can only perform this role in lower doses ( 26 , 27 ). The possible reduction in food consumption and increased physical activity together with the increased levels of insulin in the plasma could contribute to the lowered plasma glucose shown in this study. The reduction in the levels of glycated haemoglobin following exposure to nicotine may be potentially beneficial in diabetic management. This is because a reduction or control of glycated haemoglobin is an important marker in delaying or preventing diabetic complications ( 28 , 29 , 30 , 31 ). Nicotine cessation can occur when a smoker quits for some reasons. This sudden withdrawal may have many consequences including restlessness, anxiety and increase in appetite. In the present study, we examined the plasma levels of insulin, glucose and glycated haemoglobin four weeks following cessation of nicotine in wistar rats. The result showed that four weeks after cessation or withdrawal of initial 200µg/kg nicotine there were no significant changes in the levels of plasma glucose, insulin and glycated haemoglobin compared to the nicotine exposed groups. However, withdrawal, after initial exposure to 400µg/kg of nicotine was associated with significant rise in both the plasma glucose and glycated haemoglobin but no significant change in insulin compared to their respective nicotine exposed groups. Cessation, after initial exposure to high dose of nicotine (800µg/kg) resulted in significant rise in plasma levels of glucose, glycated haemoglobin and insulin compared to their nicotine exposed group. Therefore, reversal of plasma glucose and glycated haemoglobin levels could be achieved four weeks after cessation of 800µg/kg of nicotine. This result could suggest a possible association of nicotine cessation with decreased insulin sensitivity and increased insulin resistance ( 32 ). Declarations Author Contribution Study conception and design were done by O.O. Materials preparation and data collection was performed by F.N.N, O.O, L.N and S.O.O, O.O performed the statistical analysis. The first draft of the manuscript was written by L.N. A.O reviewed the manuscript. All authors commented on previous versions of the manuscript. References Dai, X., Gakidou, E., & Lopez, A. D. (2022). Evolution of the global smoking epidemic over the past half century: strengthening the evidence base for policy action. Tobacco control, 31 (2), 129–137. Kondo, T., Nakano, Y., Adachi, S., & Murohara, T. (2019). Effects of Tobacco Smoking on Cardiovascular Disease. Circulation journal: official journal of the Japanese Circulation Society, 83(10), 1980–1985. Christian, P., West, K. P., Jr, Katz, J., Kimbrough-Pradhan, E., LeClerq, S. C., Khatry, S. K., & Shrestha, S. R. (2004). Cigarette smoking during pregnancy in rural Nepal. 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A reappraisal of the blood glucose homeostat which comprehensively explains the type 2 diabetes mellitus-syndrome X complex. The Journal of physiology, 549(Pt 2), 333–346. McLaughlin, I., Dani, J. A., & De Biasi, M. (2015). Nicotine withdrawal. Current topics in behavioral neurosciences, 24, 99–123. Audrain-McGovern, J., & Benowitz, N. L. (2011). Cigarette smoking, nicotine, and body weight. Clinical pharmacology and therapeutics, 90(1), 164–168. Baraona, L. K., Lovelace, D., Daniels, J. L., & McDaniel, L. (2017). Tobacco harms, Nicotine Pharmacology, and Pharmacologic tobacco cessation interventions for women. Journal of Midwifery and Women’s Health. 62 (3): 253–269. Xu, S. H., Jin, W. S., & Lin, Y. D. (2003). Di 1 jun yi da xue xue bao = Academic journal of the first medical college of PLA, 23(8), 859–862. Bellinger, L. L., Wellman, P. J., Harris, R. B., Kelso, E. W., & Kramer, P. R. (2010). The effects of chronic nicotine on meal patterns, food intake, metabolism and body weight of male rats. Pharmacology, biochemistry, and behavior, 95(1), 92–99. Liu, M., Chuang Key, C. C., Weckerle, A., Boudyguina, E., Sawyer, J. K., Gebre, A. K., Spoo, W., Makwana, O., & Parks, J. S. (2018). Feeding of tobacco blend or nicotine induced weight loss associated with decreased adipocyte size and increased physical activity in male mice. Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association, 113, 287–295. Calarco, C. A., & Picciotto, M. R. (2020). Nicotinic Acetylcholine Receptor Signaling in the Hypothalamus: Mechanisms Related to Nicotine's Effects on Food Intake. Nicotine & tobacco research: official journal of the Society for Research on Nicotine and Tobacco, 22 (2), 152–163. Ketterly J. (2022). Sports Medicine: Ergogenic Aids. FP essentials, 518, 23–28. Poltavski, D. V., Petros, T. V., and Holm, J. E. (2012). Lower but not higher doses of transdermal nicotine facilitate cognitive performance in smokers on gender non-preferred tasks. Pharmacol. Biochem. Behav. 102, 423–433. Mündel, T. (2017). Nicotine: sporting friend or foe? A review of athlete use, performance consequences and other considerations. Sports Med. 47, 2497–2506. Obia, O., Ogwa, O. O., Ojeka, S. O., Ajah, A. A., & Chuemere, A. N. (2016). Effect of honey on the body weight of glibenclamide treated alloxan-induced diabetic wistar rats. Journal of Apitherapy. 1 (1): 33–35. Sherwani, S. I., Khan, H. A., Ekhzaimy, A., Masood, A., & Sakharkar, M. K. (2016). Significance of HbA1c Test in Diagnosis and Prognosis of Diabetic Patients. Biomarker insights, 11, 95–104. Asuquo, A. E., Obia, O., & Chuemere, A. N. (2018). Prolonged effect of Niger delta honey on blood glucose and haematological parameters in alloxan-induced diabetic rats. International Journal of Biochemistry Research and Review. 21 (4): 1–10. Casadei, G., Filippini, M., & Brognara, L. (2021). Glycated Hemoglobin (HbA1c) as a Biomarker for Diabetic Foot Peripheral Neuropathy. Diseases (Basel, Switzerland), 9(1), 16. Lee, S. S., Seo, J. S., Kim, S. R., Jeong, J. E., Nam, B. W., Lee, J. Y., Lee, H. J., Lee, C., Lee, C. U., Paik, I. H., Chae, J. H., Chai, S. H., Yoo, S. J., Won, W. Y., & Kim, D. J. (2011). The changes of blood glucose control and lipid profiles after short-term smoking cessation in healthy males. Psychiatry investigation, 8(2), 149–154. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 18 Apr, 2024 Read the published version in East African Scholars Journal of Medical Sciences → Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3917916","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":271356246,"identity":"b854d270-6619-463b-b004-519a19c79170","order_by":0,"name":"Onyebuchi Obia","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABCUlEQVRIiWNgGAWjYJACZiBOYGNgYGNIYLCBCPGQoCUNRBGphQGi9jBhLfzSPYaPC9vs8vgYmI89eFBzPnH+/AbGB2/bGPLkHbBrkZxzxth4ZltyMRsDW7pBwrHbiRuOMTAbzm1jKDY8gF2LwY0cM2netgOJbQw8ZhIJbEAtQM1AEYbEjQ04tZj/Rmj5dy5xfhsD+28CWsyY4VoSgYyGYwxszCAt83F4X3JGWrH0jHPJiW3MQL8k9iUbbziW2Cw555xE4gZcISaRvPFzQZld4vz25mMPf3yzk53ffPjghzdlNonzcTiMgYHDAEIzw0UYQWolGAwO4NLC/gCHhDxOW0bBKBgFo2CEAQDaclg9pIRzewAAAABJRU5ErkJggg==","orcid":"","institution":"Rivers State University","correspondingAuthor":true,"prefix":"","firstName":"Onyebuchi","middleName":"","lastName":"Obia","suffix":""},{"id":271356247,"identity":"572bd2b4-8ba0-466f-b0df-c103ffa45054","order_by":1,"name":"Ledu Nda-ue","email":"","orcid":"","institution":"University of Port Harcourt","correspondingAuthor":false,"prefix":"","firstName":"Ledu","middleName":"","lastName":"Nda-ue","suffix":""},{"id":271356248,"identity":"f90c8049-5f82-49a7-a3cc-e45b21809c4d","order_by":2,"name":"Sunday Ogbu Ojeka","email":"","orcid":"","institution":"University of Port Harcourt","correspondingAuthor":false,"prefix":"","firstName":"Sunday","middleName":"Ogbu","lastName":"Ojeka","suffix":""},{"id":271356249,"identity":"0b95779f-0009-49b3-b97c-a8bff22dda1b","order_by":3,"name":"Azubuike Ogba","email":"","orcid":"","institution":"University of Port Harcourt","correspondingAuthor":false,"prefix":"","firstName":"Azubuike","middleName":"","lastName":"Ogba","suffix":""},{"id":271356250,"identity":"e05d4477-efb8-4828-9008-271d83039e0c","order_by":4,"name":"Frank Nwabueze Nwokocha","email":"","orcid":"","institution":"University of Port Harcourt","correspondingAuthor":false,"prefix":"","firstName":"Frank","middleName":"Nwabueze","lastName":"Nwokocha","suffix":""}],"badges":[],"createdAt":"2024-02-01 15:29:17","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3917916/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3917916/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.36349/easms.2024.v07i04.005","type":"published","date":"2024-04-18T22:40:52+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":50847462,"identity":"ad8d1904-a02d-4a5b-88b3-ea591b702476","added_by":"auto","created_at":"2024-02-08 09:54:26","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":152856,"visible":true,"origin":"","legend":"\u003cp\u003ePlasma glucose levels in the nicotine exposure and withdrawal groups\u003c/p\u003e\n\u003cp\u003eThe symbol, # represents significant difference in plasma glucose between nicotine exposure and nicotine withdrawal.\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-3917916/v1/a2cf2e887facda74f02cd821.jpeg"},{"id":50847463,"identity":"5526756c-6be3-4f16-a8db-1f4199ae07be","added_by":"auto","created_at":"2024-02-08 09:54:26","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":174396,"visible":true,"origin":"","legend":"\u003cp\u003eComparing plasma insulin levels in the nicotine exposed and withdrawal groups\u003c/p\u003e\n\u003cp\u003eThe symbol, # represents significant difference in plasma insulin between nicotine exposure and nicotine withdrawal\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-3917916/v1/f9cbffea175c96a6976327ca.jpeg"},{"id":50847464,"identity":"3097d09a-01a9-4781-a3c3-75ce79655108","added_by":"auto","created_at":"2024-02-08 09:54:26","extension":"jpeg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":188728,"visible":true,"origin":"","legend":"\u003cp\u003eComparing plasma glycated hemoglobin levels in the nicotine exposed and withdrawal groups\u003c/p\u003e\n\u003cp\u003eThe symbol, # represents significant difference in plasma glycated hemoglobin levels between nicotine exposure and nicotine withdrawal groups.\u003c/p\u003e","description":"","filename":"floatimage3.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-3917916/v1/c5500af4cc288f41589d1153.jpeg"},{"id":55690595,"identity":"2c7a8002-6e2a-4fec-9647-e36ed822e1fd","added_by":"auto","created_at":"2024-05-01 22:40:56","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":436108,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3917916/v1/4d271cef-db5f-43f0-b456-e0e605e8b1c5.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Impact of Nicotine Exposure and withdrawal on Plasma glucose, insulin and glycated haemoglobin in high-fat diet fed wistar rats","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eThe global prevalence of cigarette smoking has remained unabated over the years (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) despite all the campaigns staged against it. Studies have associated higher risk of cardiovascular disorders and other conditions with cigarette smoking (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Although some studies suggest that combining exercise or dietary factors could mitigate the risk of disease in cigarette smokers (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e), it has remained a leading cause of preventable death globally (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). The most abundant constituent of tobacco cigarette is nicotine which has proven addictive effect on smokers, making it one of the most commonly abused drugs (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Nicotine binds to nicotinic cholinergic receptors to stimulate the release of dopamine and thus adrenaline (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). The drug has significant effects on attention and memory (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). However, sudden withdrawal of nicotine has been associated with reversible impairment of attention and memory (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eObesity, a global epidemic and major public health concern is basically characterized by excessive body fat accumulation. Comparatively, the prevalence of obesity amongst smokers is lower than that of non-smokers (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). Although, obesity alone is associated with increased risk of cardio-metabolic disorders. However, obesity paired with tobacco smoking further increases the risk of cardio-metabolic disorders and represent the largest challenges to public health (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). The causal correlation between nicotine and obesity is poorly understood, thus necessitating this study. Eating and smoking are behavioural traits that are to an extent controlled by the same reward mechanism (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). Studies have shown that nicotine may interfere with glucose-regulating mechanisms of the body (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). Withdrawal of nicotine as in quitting of cigarette smoking can result in intense cravings for nicotine, irritability, depression, insomnia, hunger, and difficulty concentrating (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). The increased appetite associated with nicotine withdrawal could be due to reactivation of pathways that were previously blocked by nicotine (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). Studies suggest that the nicotine withdrawal symptoms could result from the brain having no opposing force (dopamine) to dampen its effects. It is the lack of this opposing force that causes withdrawal symptoms (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe aim of the present study was to investigate the effects of nicotine exposure and discontinuation on serum insulin, glucose and glycated haemoglobin of high-fat diet fed wistar rats.\u003c/p\u003e"},{"header":"MATERIALS AND METHODS","content":"\u003cp\u003e This study was carried out in the department of Human Physiology, Faculty of Basic Medical Sciences, University of Port Harcourt with ethical approval number: UPH/CEREMAD/REC/MM68/053. The experiment involved 48 male wistar rats separated into 4 groups of 8 rats each which were acclimatized for a period of two weeks being provided with standard animal chow and water \u003cem\u003ead libitum\u003c/em\u003e. After acclimatization, all the animals were placed on high-fat diet (Margarine; blue band) in addition to the different doses of nicotine in the experimental groups. Group 1 served as control and received distilled water, Groups 2, 3 and 4 received 200\u0026micro;g/kg, 400\u0026micro;g/kg and 800\u0026micro;g/kg of nicotine oral solution respectively. The experiment was performed in two phases. In the first phase, the experimental groups were placed on their respective doses of nicotine solution for 4 weeks. Thereafter, 4 animals in each group were sacrificed and blood samples collected to determine their nicotine exposure plasma levels of glucose, insulin and glycated hemoglobin. In the second phase of the experiment, nicotine was discontinued in the experimental groups. The remaining 4 animals in each group continued without nicotine for another four weeks after which they were sacrificed and blood samples collected to determine their nicotine withdrawal plasma levels of glucose, insulin and glycated hemoglobin. All the parameters were determined using standard methods and values recorded.\u003c/p\u003e \u003cp\u003eData were analyzed using SPSS vs 23 and presented in Tables and graphs. Continuous variables were expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SEM. The differences between each group were analyzed using paired sample t-test and ANOVA. Values of \u003cem\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.05\u003c/em\u003e were considered significant with a confidence level of 95%.\u003c/p\u003e"},{"header":"RESULTS AND DISCUSSION","content":"\u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eEffect of nicotine exposure on plasma glucose, insulin, and glycated hemoglobin of wistar rats\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGroups\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGlucose (mmol/l)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eInsulin (IU/l)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHbA1\u003csub\u003ec\u003c/sub\u003e (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eControl\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e7.78\u0026thinsp;\u0026plusmn;\u0026thinsp;0.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e10.70\u0026thinsp;\u0026plusmn;\u0026thinsp;0.77\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e6.50\u0026thinsp;\u0026plusmn;\u0026thinsp;0.08\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e200\u0026micro;g/kg of nct\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e6.63\u0026thinsp;\u0026plusmn;\u0026thinsp;0.49*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e14.90\u0026thinsp;\u0026plusmn;\u0026thinsp;1.07*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e5.75\u0026thinsp;\u0026plusmn;\u0026thinsp;0.32*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e400\u0026micro;g/kg nct\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e5.35\u0026thinsp;\u0026plusmn;\u0026thinsp;0.34*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e18.88\u0026thinsp;\u0026plusmn;\u0026thinsp;0.28*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e4.95\u0026thinsp;\u0026plusmn;\u0026thinsp;0.22*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e800\u0026micro;g/kg of nct\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e4.73\u0026thinsp;\u0026plusmn;\u0026thinsp;0.19*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e15.88\u0026thinsp;\u0026plusmn;\u0026thinsp;0.45*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e4.55\u0026thinsp;\u0026plusmn;\u0026thinsp;0.13*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eValues are mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard error of mean\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e*Significant compared to control.\u003c/p\u003e \u003cp\u003enct; nicotine.\u003c/p\u003e \u003cp\u003eThere was dose-dependent reduction in plasma glucose and glycosylated hemoglobin levels following exposure to nicotine. Whereas the plasma insulin levels increased significantly compared to control in high-fat diet fed wistar rats.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eWithdrawal effects of nicotine on plasma glucose, insulin and glycated hemoglobin.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGroups\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGlucose (mmol/l)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eInsulin (IU/l)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHbA1\u003csub\u003ec\u003c/sub\u003e (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eControl\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e6.95\u0026thinsp;\u0026plusmn;\u0026thinsp;0.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e16.30\u0026thinsp;\u0026plusmn;\u0026thinsp;0.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e5.98\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e200\u0026micro;g/kg of nct\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e5.68\u0026thinsp;\u0026plusmn;\u0026thinsp;0.41*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e17.80\u0026thinsp;\u0026plusmn;\u0026thinsp;2.46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e5.18\u0026thinsp;\u0026plusmn;\u0026thinsp;0.26*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e400\u0026micro;g/kg nct\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e6.90\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e21.15\u0026thinsp;\u0026plusmn;\u0026thinsp;1.57*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e6.20\u0026thinsp;\u0026plusmn;\u0026thinsp;0.24\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e800\u0026micro;g/kg of nct\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e7.35\u0026thinsp;\u0026plusmn;\u0026thinsp;0.27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e22.75\u0026thinsp;\u0026plusmn;\u0026thinsp;0.93*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e6.28\u0026thinsp;\u0026plusmn;\u0026thinsp;0.17\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eValues are mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard error of mean\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e*Significant compared to control.\u003c/p\u003e \u003cp\u003enct; nicotine.\u003c/p\u003e \u003cp\u003eThere was significant reduction in plasma glucose and glycosylated hemoglobin with the lowest dose of nicotine following withdrawal but no significant effect with the higher doses. Whereas the plasma insulin levels increased significantly with the higher doses following nicotine withdrawal in high-fat diet fed wistar rats.\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eNicotine which is commonly used as a recreational drug is known to possess highly addictive properties. The present study examined the effect of nicotine exposure on the glycemia of high fat-diet fed wistar rats. The results showed that exposure to the three concentrations of nicotine (200, 400 and 800\u0026micro;g/kg respectively) significantly caused a rise in plasma insulin levels but reduction in both plasma glucose and glycated haemoglobin levels compared to their control group. Physiologically, insulin is known to drive glucose into the cells and therefore has an inverse relationship with plasma glucose (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e). The reduction in both the plasma glucose and glycated haemoglobin were in a dose-dependent fashion. Previous studies have linked continues exposure to nicotine with increases in basal metabolic rate, thermogenesis and physical activity but reduction in food intake (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). Most of the stimulants of the central nervous system are often used as ergogenic aids (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e) which increases energy utilization in endurance exercises. However, studies suggest that nicotine as a CNS stimulant can only perform this role in lower doses (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e). The possible reduction in food consumption and increased physical activity together with the increased levels of insulin in the plasma could contribute to the lowered plasma glucose shown in this study. The reduction in the levels of glycated haemoglobin following exposure to nicotine may be potentially beneficial in diabetic management. This is because a reduction or control of glycated haemoglobin is an important marker in delaying or preventing diabetic complications (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eNicotine cessation can occur when a smoker quits for some reasons. This sudden withdrawal may have many consequences including restlessness, anxiety and increase in appetite. In the present study, we examined the plasma levels of insulin, glucose and glycated haemoglobin four weeks following cessation of nicotine in wistar rats. The result showed that four weeks after cessation or withdrawal of initial 200\u0026micro;g/kg nicotine there were no significant changes in the levels of plasma glucose, insulin and glycated haemoglobin compared to the nicotine exposed groups. However, withdrawal, after initial exposure to 400\u0026micro;g/kg of nicotine was associated with significant rise in both the plasma glucose and glycated haemoglobin but no significant change in insulin compared to their respective nicotine exposed groups. Cessation, after initial exposure to high dose of nicotine (800\u0026micro;g/kg) resulted in significant rise in plasma levels of glucose, glycated haemoglobin and insulin compared to their nicotine exposed group. Therefore, reversal of plasma glucose and glycated haemoglobin levels could be achieved four weeks after cessation of 800\u0026micro;g/kg of nicotine. This result could suggest a possible association of nicotine cessation with decreased insulin sensitivity and increased insulin resistance (\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e).\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eStudy conception and design were done by O.O. Materials preparation and data collection was performed by F.N.N, O.O, L.N and S.O.O, O.O performed the statistical analysis. The first draft of the manuscript was written by L.N. A.O reviewed the manuscript. All authors commented on previous versions of the manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eDai, X., Gakidou, E., \u0026amp; Lopez, A. D. (2022). Evolution of the global smoking epidemic over the past half century: strengthening the evidence base for policy action. Tobacco control, \u003cem\u003e31\u003c/em\u003e(2), 129\u0026ndash;137.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKondo, T., Nakano, Y., Adachi, S., \u0026amp; Murohara, T. (2019). Effects of Tobacco Smoking on Cardiovascular Disease. Circulation journal: official journal of the Japanese Circulation Society, 83(10), 1980\u0026ndash;1985.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChristian, P., West, K. P., Jr, Katz, J., Kimbrough-Pradhan, E., LeClerq, S. C., Khatry, S. K., \u0026amp; Shrestha, S. R. (2004). Cigarette smoking during pregnancy in rural Nepal. Risk factors and effects of beta-carotene and vitamin A supplementation. European journal of clinical nutrition, 58(2), 204\u0026ndash;211.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eObia, O., Efone, P. E., \u0026amp; Wichendu, P. N. (2015). Effect of Exercise on the Blood Pressure of Cigarette Smokers. The International journal of innovative research and development, 4 (8), 88\u0026ndash;90.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWorld Health Organization. (2019). WHO report on the global tobacco epidemic 2019: \u003cem\u003eoffer help to quit tobacco use\u003c/em\u003e. Geneva: World Health Organization; 2019. [accessed Feb 22, 2021].\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGrana, R., Benowitz, N., \u0026amp; Glantz, S. A. (2014). E-cigarettes: a scientific review. Circulation, 129(19), 1972\u0026ndash;1986.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSajja, R. K., Rahman, S., \u0026amp; Cucullo, L. (2016). Drugs of abuse and blood-brain barrier endothelial dysfunction: A focus on the role of oxidative stress. Journal of cerebral blood flow and metabolism: official journal of the International Society of Cerebral Blood Flow and Metabolism, 36(3), 539\u0026ndash;554.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBenowitz N. L. (2009). Pharmacology of nicotine: addiction, smoking-induced disease, and therapeutics. Annual review of pharmacology and toxicology, 49, 57\u0026ndash;71.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLoi, B., Sahai, M. A., De Luca, M. A., Shiref, H., \u0026amp; Opacka-Juffry, J. (2020). The Role of Dopamine in the Stimulant Characteristics of Novel Psychoactive Substances (NPS)-Neurobiological and Computational Assessment Using the Case of Desoxypipradrol (2-DPMP). Frontiers in pharmacology, 11, 806.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHeishman, S. J., Kleykamp, B. A., \u0026amp; Singleton, E. G. (2010). Meta-analysis of the acute effects of nicotine and smoking on human performance. Psychopharmacology, 210(4), 453\u0026ndash;469.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eValentine, G., \u0026amp; Sofuoglu, M. (2018). Cognitive Effects of Nicotine: Recent Progress. Current neuropharmacology, 16(4), 403\u0026ndash;414.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBruijnzeel A. W. (2012). Tobacco addiction and the dysregulation of brain stress systems. Neuroscience and biobehavioral reviews, 36(5), 1418\u0026ndash;1441.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGinawi, I., Bashir, A., Alreshidi, Y., Dirweesh, A., Al-Hazimi, A., Ahmed, H., Kamal, E., \u0026amp; Ahmed, M. (2016). Association Between Obesity and Cigarette Smoking: A Community-Based Study. Journal Of Endocrinology and Metabolism, 6(5), 149\u0026ndash;153.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRupprecht, L. E., Kreisler, A. D., Spierling, S. R., de Guglielmo, G., Kallupi, M., George, O., Donny, E. C., Zorrilla, E. 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Biomarker insights, 11, 95\u0026ndash;104.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAsuquo, A. E., Obia, O., \u0026amp; Chuemere, A. N. (2018). Prolonged effect of Niger delta honey on blood glucose and haematological parameters in alloxan-induced diabetic rats. International Journal of Biochemistry Research and Review. 21 (4): 1\u0026ndash;10.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCasadei, G., Filippini, M., \u0026amp; Brognara, L. (2021). Glycated Hemoglobin (HbA1c) as a Biomarker for Diabetic Foot Peripheral Neuropathy. Diseases (Basel, Switzerland), 9(1), 16.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLee, S. S., Seo, J. S., Kim, S. R., Jeong, J. E., Nam, B. W., Lee, J. Y., Lee, H. J., Lee, C., Lee, C. U., Paik, I. H., Chae, J. H., Chai, S. H., Yoo, S. J., Won, W. Y., \u0026amp; Kim, D. J. (2011). The changes of blood glucose control and lipid profiles after short-term smoking cessation in healthy males. Psychiatry investigation, 8(2), 149\u0026ndash;154.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Nicotine, Plasma glucose, insulin, glycated haemoglobin, high-fat diet","lastPublishedDoi":"10.21203/rs.3.rs-3917916/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3917916/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground to the study\u003c/strong\u003e: Nicotine, which is the most abundant constituent of tobacco cigarette is one of the most commonly abused drugs. The duo of obesity and tobacco smoking increases the risk of cardiometabolic disorders.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethodology\u003c/strong\u003e: The experiment involved 48 male wistar rats separated into 4 groups of 8 rats each. All the animals were placed on high-fat diet (Margarine; blue band) in addition to the different doses of nicotine in the experimental groups. Group 1 served as control and received distilled water, Groups 2, 3 and 4 received 200µg/kg, 400µg/kg and 800µg/kg of nicotine oral solution respectively. The experimental groups were placed on their respective doses of nicotine solution for an initial four weeks. Thereafter, four animals in each group were sacrificed and blood samples collected to determine their nicotine exposure plasma levels of glucose, insulin and glycated hemoglobin. The remaining four animals in each group continued without nicotine for another four weeks after which they were sacrificed and blood samples collected to determine their nicotine withdrawal plasma levels of glucose, insulin and glycated hemoglobin.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: The results showed that exposure to the three concentrations of nicotine (200, 400 and 800µg/kg respectively) significantly caused a rise in plasma insulin levels but dose-dependent reduction in both glucose and glycated haemoglobin compared to their control groups. Four weeks after withdrawal of initial 200µg/kg nicotine there were no significant changes in the levels of plasma glucose, insulin and glycated haemoglobin compared to the nicotine exposed groups. Withdrawal, after initial exposure to 400µg/kg of nicotine was associated with significant rise in both the plasma glucose and glycated haemoglobin but no significant change in insulin compared to their respective nicotine exposed groups. Cessation, after initial exposure 800µg/kg of nicotine resulted in significant rise in plasma levels of glucose, glycated haemoglobin and insulin compared to their nicotine exposed groups.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e: The possible reduction in food consumption and increased physical activity together with the increased levels of insulin in the plasma could contribute to the lowered plasma glucose shown in this study. The reduction in the levels of glycated haemoglobin following exposure to nicotine may be potentially beneficial in diabetic management. Therefore, reversal of plasma glucose and glycated haemoglobin levels could be achieved four weeks after cessation of 800µg/kg of nicotine. This result could suggest a possible association of nicotine cessation with decreased insulin sensitivity.\u003c/p\u003e","manuscriptTitle":"Impact of Nicotine Exposure and withdrawal on Plasma glucose, insulin and glycated haemoglobin in high-fat diet fed wistar rats","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-02-08 09:54:21","doi":"10.21203/rs.3.rs-3917916/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"a2dbcd0e-75aa-4d93-b902-8837badd5896","owner":[],"postedDate":"February 8th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-05-01T22:40:52+00:00","versionOfRecord":{"articleIdentity":"rs-3917916","link":"https://doi.org/10.36349/easms.2024.v07i04.005","journal":{"identity":"east-african-scholars-journal-of-medical-sciences","isVorOnly":true,"title":"East African Scholars Journal of Medical Sciences"},"publishedOn":"2024-04-18 22:40:52","publishedOnDateReadable":"April 18th, 2024"},"versionCreatedAt":"2024-02-08 09:54:21","video":"","vorDoi":"10.36349/easms.2024.v07i04.005","vorDoiUrl":"https://doi.org/10.36349/easms.2024.v07i04.005","workflowStages":[]},"version":"v1","identity":"rs-3917916","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3917916","identity":"rs-3917916","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}