Crocin stimulates insulin secretion via the activation of K+ and Ca2+ channels, and inhibits carbohydrate digestion and absorption, and DPPH

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Data may be preliminary. 16 May 2025 V1 Latest version Share on Crocin stimulates insulin secretion via the activation of K+ and Ca2+ channels, and inhibits carbohydrate digestion and absorption, and DPPH Author : Asma Ahammed Authors Info & Affiliations https://doi.org/10.22541/au.174737369.98827055/v1 410 views 215 downloads Contents Abstract Supplementary Material Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract This study investigated crocin’s role in promoting insulin secretion and explored the underlying mechanisms involved.Insulin secretory effects of crocin were assessed in a perfused rat pancreas. To investigate the pathways involved in insulin release, experiments were conducted with 11 mM glucose, 50 µM verapamil, 8 mM diazoxide, and 200 µM IBMX. Sucrose malabsorption was measured in six GI tract segments of rats after administering an oral sucrose load. Glucose absorption was evaluated through in situ intestinal perfusion (from duodenum to 40 cm); in vitro starch digestion using α-amylase and α-glucosidase enzymes and glucose diffusion via a cellulose ester dialysis membrane. Crocin’s antioxidant potential was tested through DPPH radical inhibition assays. Gastrointestinal motility was assessed using the BaSO₄ milk transit test. Crocin induced a fourfold rise in insulin secretion in the perfused rat pancreas.Crocin, combined with 11 mM glucose, significantly increased insulin release. Insulin secretion induced by crocin was significantly reduced by diazoxide (KATP opener) and verapamil (Ca²⁺ channel blocker), indicating involvement of glucose metabolism, calcium signaling, and KATP channels. Insulin release was not increased by crocin in the presence of IBMX, suggesting a mechanism independent of the adenylate cyclase–cAMP signaling pathway. Crocin reduced glucose absorption and increased residual sucrose levels in the intestine after oral administration. It also decreased glucose absorption during in situ intestinal perfusion with glucose and in the in vitro glucose diffusion assay. Significant enhancement in gut motility was also observed. Crocin lowered glucose release from starch digestion in vitro and demonstrated antioxidant activity by inhibiting DPPH. Crocin stimulates insulin secretion via the activation of K + and Ca 2+ channels, and inhibits carbohydrate digestion and absorption, and DPPH Asma Ahammed 1 , JMA Hannan 1 and PR Flat 2 1 Department of Pharmacy, Independent University, Bangladesh (IUB), Dhaka, Bangladesh 2 School of Biomedical Sciences, Ulster University, Co. Londonderry, Northern Ireland BT52 1SA, UK. Corresponding Author: JMA Hannan, PhD Department of Pharmacy, Independent University, Bangladesh (IUB). Dhaka, Bangladesh Email: [email protected] Cell no. +8801736734405 Abstract Crocin, extracted from Crocus sativus L., has shown blood glucose-lowering effects in both animal and human studies. This study investigated crocin’s role in promoting insulin secretion and explored the underlying mechanisms involved. To evaluate crocin’s impact on carbohydrate digestion and absorption, its free radical scavenging ability using DPPH was assessed through both in vitro and in vivo assays. Insulin secretory effects of crocin were assessed in a perfused rat pancreas. To investigate the pathways involved in insulin release, experiments were conducted with 11 mM glucose, 50 µM verapamil, 8 mM diazoxide, and 200 µM IBMX. Sucrose malabsorption was measured in six GI tract segments of rats after administering an oral sucrose load. Glucose absorption was evaluated through in situ intestinal perfusion (from duodenum to 40 cm); in vitro starch digestion using α-amylase and α-glucosidase enzymes and glucose diffusion via a cellulose ester dialysis membrane. Crocin’s antioxidant potential was tested through DPPH radical inhibition assays. Gastrointestinal motility was assessed using the BaSO₄ milk transit test. Crocin induced a fourfold rise in insulin secretion in the perfused rat pancreas. Crocin, combined with 11 mM glucose, significantly increased insulin release. Insulin secretion induced by crocin was significantly reduced by diazoxide (KATP opener) and verapamil (Ca²⁺ channel blocker), indicating involvement of glucose metabolism, calcium signaling, and KATP channels. Insulin release was not increased by crocin in the presence of IBMX, suggesting a mechanism independent of the adenylate cyclase–cAMP signaling pathway. Crocin reduced glucose absorption and increased residual sucrose levels in the intestine after oral administration. It also decreased glucose absorption during in situ intestinal perfusion with glucose and in the in vitro glucose diffusion assay. : A significant enhancement in gut motility was also observed. Crocin also lowered glucose release from starch digestion in vitro and demonstrated antioxidant activity by inhibiting DPPH. In conclusion, crocin exhibits promising antidiabetic properties and may serve as a natural therapeutic agent in diabetes management. Keywords: Crocin; Diabetes; Insulin secretion; Carbohydrate digestion and absorption; DPPH. Introduction Diabetes has become a critical global public health challenge, reaching epidemic levels worldwide [1]. The International Diabetes Federation estimates that global diabetes cases will increase from 366 million in 2011 to 552 million by 2030 [2]. Approximately 90% of diabetic patients suffer from Type 2 diabetes [3]. Type 1 diabetes accounts for 5-10% of all diabetes cases worldwide [4]. The pathogenesis of type 2 diabetes involves 4 major metabolic abnormalities: obesity, impaired insulin action, insulin secretory dysfunction, and increased endogenous glucose output (EGO) [5]. Deficient insulin secretion, insulin resistance, and poor compensatory insulin responses can lead to complications such as neuropathy, nephropathy, retinopathy, cardiovascular disease (CVD), and peripheral artery disease (PAD) [6] [7]. To obtain optimal metabolic control in diabetes, the combination of changes in lifestyle and pharmacological treatment is necessary [8]. Conventional treatments for hyperglycemia include sulfonylureas (enhance insulin release from pancreatic islets), biguanides (reduce hepatic glucose production), PPARγ agonists (boost insulin action), and α-glucosidase inhibitors (interfere with glucose absorption in the gut) [9]. These conventional antidiabetic medicines are effective but come with unavoidable side effects [10]. On the other hand, Plants are the foundation for the development of modern drugs, and medicinal herbs have been utilized for many years in everyday life to treat disease all over the world [11]. Medicinal plants contain a variety of phytoconstituents with antidiabetic effects, such as terpenoids, saponins, flavonoids, carotenoids, alkaloids, and glycosides [12]. The anti-hyperglycemic effects of treatment with plants are frequently related to their ability to increase the performance of pancreatic tissue, which is done by increasing insulin secretion or limiting intestinal glucose absorption [13]. Recent pharmacological research has demonstrated the anti-diabetic characteristics of tropical medicinal plants and vitamins, including antihyperglycemic, antilipidemic, hypoglycemic, and insulin-mimicking [14] [15]. Crocin (digentiobiosyl 8,8’-diapocarotene-8,8’-oate; C44H64O24), a type of water-soluble carotenoid pigment, is a group of polyene dicarboxylic acid, mono and di-glucosyl esters of crocetin, which are the main color-causing components of saffron and gardenia and are mostly found in Crocus sativus L. and Gardenia jasminoides Ellis. Crocin displays a broad spectrum of pharmacological activities, including protective effects against neurodegenerative, cardiovascular, cerebrovascular, hepatic, and metabolic disorders, as well as cancer and depression [16][17]. Some other phytochemicals have been isolated from different fractions of saffron, including picrocrocin, safranal, kaempferol, phenol, flavonoid, delphinidin, and crocetin, which show good bioactivity and antioxidant capacity [18]. Preclinical studies demonstrate that crocin significantly reduces serum glucose, advanced glycation end products, triglycerides, total cholesterol, and LDL, while increasing HDL levels [19]. It also claims that treatment with crocin can improve plasma levels of glucose, insulin, hemoglobin A1c, systolic blood pressure, insulin resistance, and insulin sensitivity [20]. Another study shows crocin can protect liver from damage against the toxic effects of morphine due to its antioxidant properties [21]. Crocin has been reported to have other pharmacological properties, including antidepressant [22]), anti-inflammatory [23], antioxidant [24] and antidiabetic effects [25]. This study investigates the impact of crocin on insulin secretion, carbohydrate digestion, and glucose absorption to elucidate its antidiabetic potential and mechanisms involved in glycemic regulation. 2. Materials and methods 2.1 Crocin Crocin (digentiobiosyl 8,8’-diapocarotene-8,8’-oate; C44H64O24), a type of water-soluble carotenoid pigment, the main component of saffron, was collected from Sigma, USA. 2.2 Experimental animals and induction of diabetes Male Long-Evans rats (200 - 230 g) bred at the ICDDR,B laboratory, Bangladesh, were used for this study. The animals were maintained on a 12-hour light-dark cycle at room temperature, fed on a standard laboratory pellet diet, and provided with water supplied ad libitum. Adult male Long-Evans rats weighing 180 - 220 g were used throughout the study. Type 1 diabetes was induced by a single intraperitoneal injection of streptozotocin (STZ) (65 mg/kg bw) to anaesthetized, fasted, healthy adult (3-4 months) rats (180-220 g bw). The blood glucose level was checked on the 7th day after the injection of STZ. Animals with high blood glucose levels (>20 mM) were considered type 1 diabetic. 2.3 Insulin secretion from the perfused rat pancreas Long-Evans male rats (180–250 g body weight (b.w.)) were anaesthetised with sodium-pentobarbital (50 mg/kg, intraperitoneal), and the pancreas was isolated and perfused at 37°C according to the method of [26]. KRB buffer supplemented with 1·25 g/l bovine serum albumin and 40 g/l dextran T70 and 2·8- or 11- mm glucose. A mixture of O 2 : CO 2 (95 : 5) was continuously used to gas the perfusate. The perfusate composition was changed after the first 20 min of equilibration. Samples were stored at –20°C before measurement of insulin using a rat insulin ELISA kit (Crystal Chem, USA). 2.4 Residual gut sucrose content Sucrose solution (2.5 g/kg body weight) with or without crocin (100 mg/kg) was fed to the twenty-hour fasted rats. Blood samples were obtained from the tail tip before and 30, 60, 120, and 240 min after sucrose administration for the determination of glucose, and some of the rats were sacrificed. The gastrointestinal tract was excised, and glucose was measured by the glucose-oxidase (GOD-PAP) method using a commercial kit (Boeringer Mannheim GmbH kit, Germany). 2.5 Intestinal glucose absorption An intestinal perfusion technique [27] was used to study the effect of crocin on the intestinal absorption of glucose in type 1 rats fasted for 36 h and anesthetized with sodium pentobarbital (50 mg/ kg). Crocin was added to a Kreb solution (g/l, 1.02 CaCl 2 , 7.37 NaCl, 0.20 KCl, 0.065 NaH 2 PO 4 ·6H 2 O, 0.6 NaHCO 3 , pH 7.5), supplemented with glucose (54.0 g/l) and perfused through the pyloric entry of duodenum at a perfusion rate of 0.5 ml/min for 30 min through the duodenum. The perfusate was collected from a catheter set at 40 cm. Crocin was added to the Krebs solution to a final concentration of 5 mg/ml for crocin, so that the amount of crocin in the perfused intestine would be equivalent to 100 mg/kg. The control group was perfused only with Krebs solution supplemented with glucose. The effect of Metformin (5 mg/ml in Krebs solution), a known inhibitor of glucose absorption, was tested similarly [28]. Glucose concentration was estimated by the glucose oxidase method using a commercial kit from Sera Pak, USA. The results were expressed as a percentage of absorbed glucose, calculated from the amount of glucose in the solution before and after the perfusion. 2.6 Gastrointestinal motility Gastrointestinal motility was evaluated by using Barium sulfate milk by the method previously described by [29]. BaSO 4 milk was prepared by adding BaSO 4 (10% w/v) in 0.5% CMC suspension. The milk was given to a group of rats after 1 h of administration of crocin. The treated rats were sacrificed 15 minutes after the administration of the milk. The distance traversed by BaSO 4 milk was measured and expressed as a percentage of the total length of the small intestine (from pylorus to the ileocecal junction) and compared with the control group administered distilled water. 2.7 in vitro starch digestion A starch solution (2 mg/ml; 100 mg in 50 ml, Sigma Aldrich, St. Louis, MO, USA) was incubated with or without crocin (5 – 50 mg/ml) and acarbose (5 – 50 mg/ml) in the presence of 0.01% heat-stable α-amylase and 0.1% amyl glucosidase (Sigma Aldrich) at 80°C for 20 minutes and at 60°C for 30 minutes. Glucose liberation was analyzed using the Glucose Oxidase-Peroxidase (GOD-PAP) reagent for the assessment of potential inhibitory effects of crocin on carbohydrate digestion [30]. 2.8 in vitro glucose diffusion The in vitro glucose diffusion and absorption assay was evaluated using a cellulose ester dialysis tube (CEDT) (20 cm × 7.5 mm, Spectra/Por® CE layer, MWCO: 2000, Spectrum, Breda, The Netherlands). Each dialysis tube was carefully filled with 2 ml of a solution containing 0.9% sodium chloride (NaCl) and 220 mM glucose, in the presence of crocin at concentrations ranging from 5 to 50 mg/ml. Acarbose (5 to 50 mg/ml) was used as a standard drug. The ends of the tubes were securely sealed to prevent leakage, and the CEDT was subsequently placed in 50 ml Falcon conical tubes (Orange Scientific, Northern Orange County, CA, USA) containing 45 ml of 0.9% NaCl. The tubes were then incubated at 37°C in an orbital shaker to maintain continuous agitation and facilitate diffusion. Glucose levels were measured at multiple time points, including 0, 0.5, 1, 2, 4, and 6 hours, to assess the impact of crocin on glucose transport across the membrane [30]. 2.9 in vitro DPPH Assay The free radical scavenging activity of crocin was evaluated by estimating percentage inhibition of 2,2-Diphenyl-1-picrylhydrazyl (DPPH). Stock solutions of crocin and the standard antioxidant, L-ascorbic acid, were prepared at varying concentrations ranging from 50 to 2000 µg/ml. For each concentration, 1 ml of the sample or standard was mixed with 2 ml of a freshly prepared 0.2 mmol/l DPPH solution, which was dissolved in methanol to maintain stability. A control solution was prepared using 2 mL of 0.2 mmol/l DPPH solution combined with 1 ml of distilled water to determine the baseline absorbance. All reaction mixtures were incubated in complete darkness for 30 minutes at room temperature to ensure adequate interaction between antioxidants and free radicals. The absorbance of the samples was recorded at 517 nm using a UV/VIS spectrophotometer (Mettler-Toledo, Columbus, OH, USA). The percentage of DPPH radical scavenging was calculated to determine the antioxidant potential of crocin. % inhibition = [(AC - AOD)/AC] × 100, where AC is the absorbance of the control and AOD is the absorbance of the test drug. 2.10 Statistical analysis Results are presented as mean ± SEM for a given number of observations (n). Data from each set of observations were cross-compared using an unpaired Student’s t test, and the Mann-Whitney U test was appropriate (SPSS for Windows). Where data were collected over several time points, they have been analysed using repeated measures ANOVA, with Bonferroni adjustment to ensure an overall error rate of 5%. One-way ANOVA was performed, and pair-wise comparisons to the control group were performed using Dunnett’s test to preserve an overall error rate of 5%. Differences were considered significant if p<0.05. 3. Results 3.1 Effects of crocin on insulin secretion from the perfused pancreas In control perfusion, the pancreas retained the normal insulin secretory capacity during 70 min of the experiment with exposure to glucose and arginine. This revealed a 3-fold increase in insulin release in response to 19 mM arginine compared to 11 mM glucose (Fig. 1). Baseline values from the control and crocin experiments overlapped. Crocin produced a biphasic increase in insulin release with a 4-fold elevation above the basal level (2·8 mm) (Fig. 2). Subsequent exposure of 10 min to 11 mm glucose caused a sharp rise in insulin release from the basal level. After adding crocin to 11 mm glucose, a further enhancement in insulin release was noted (Fig. 3). As shown in Fig. 4 and Fig. 5, perfusion in the presence of verapamil and diazoxide at 11 mm glucose decreased the insulin-releasing activity of the crocin by 16–20 %. Addition of IBMX (100 mm) to crocin did not increase insulin secretion further (Fig. 6). 3.2 Effects of crocin on sucrose tolerance Sucrose ingestion caused an elevation in blood glucose with a peak of 30 min and then decreased gradually in type 1 rats. The rise in blood glucose after sucrose loading was significantly suppressed by the simultaneous administration of acarbose at 30, 60 and 120 min (p< 0.01 – 0.001); and crocin at 30, 60 and 120 min (p< 0.05 – 0.01) in type 1 diabetic rats (Fig 7). 3.3 Effects of crocin on unabsorbed sucrose content in the gut After administration of sucrose, it remained in the stomach (35.1±1.2 mg), upper (4.0±1.1 mg), middle (11.2±1.9 mg), and lower (2.2±0.9 mg) small intestine at 1 hour. When acarbose was administered simultaneously with the sucrose load, the residual sucrose content in the gastrointestinal tract increased significantly (p<0.05 – 0.001), especially in the upper intestine at 30 min, in the whole intestine as well as the cecum at 1 hr and 2 hr. Crocin increased remaining sucrose significantly (p<0.05 – 0.01) in the whole intestine as well as the cecum at 30 min and 60 min. At 4 hours, sucrose was not detected in the gut in both groups (Fig. 8). 3.4. Effects of crocin on intestinal glucose absorption The intestinal glucose absorption was almost constant during 30 min of perfusion with glucose. When the crocin was supplemented with the glucose solution, the percentage absorption of glucose decreased by 10-13% during the whole perfusion period (p<0.05 – 0.01). Metformin, a standard drug inhibitor of glucose transport across the small intestine, significantly (p< 0.01 – 0.001) decreased glucose absorption during the whole perfusion period compared with the control (Fig 9). 3.5 Effects of crocin on gastrointestinal motility After the administration of barium milk, the percentage of length traversed by the milk increased by 22% in Crocin-fed rats compared to control rats (p<0.05, Fig 10). Standard drugs, Hyocine butyl bromide, increased GI motility by 33%, and sennoside decreased by 40%. 3.6 Effect of crocin on starch digestion in vitro Figure-11 demonstrates the concentration-dependent effects of acarbose (5 – 50 mg/ml) and Crocin (5 – 50 mg/ml) on starch digestion. Acarbose, used as a positive control, showed a marked dose-dependent inhibition of glucose release (70% to 80%) at increasing concentrations (5 – 50 mg/ml) (p<0.05 - 0.001). Crocin resulted in a significant (p<0.05 – 0.01) reduction in glucose liberation, ranging from 25% to 30%, in a concentration-dependent manner (10 – 50 mg/ml). 3.7 Effect of crocin on glucose diffusion in vitro The inhibition of glucose absorption by Acarbose (5 to 50 mg/ml) was observed at 30 min, 1 hr, 2 hr, 4 hr, and 6 hr (p<0.05 – 0.01) in a dose-dependent manner by 10 - 30% at concentrations of 5 to 50 mg/ml. Crocin inhibited glucose absorption at 1 hr, 2 hr, 4 hr and 6 hr (p<0.05 – 0.01) in a dose-dependent manner by 6 – 18% at concentrations of 5 to 50 mg/ml (Fig 12). 3.8 Effect of crocin on DPPH activity in vitro Crocin effectively scavenged DPPH activity in a dose-dependent manner, by 42.17 ± 1.51% to 83.23 ± 1.82% at concentrations ranging from 50 to 2000 µg/ml (p< 0.01 – 0.001) (Table 1). Similarly, L-ascorbic acid exhibited a strong suppression of DPPH activity, with reductions ranging from 80.84 ± 1.6% to 95.84 ± 1.37% across the same concentration range (50 to 2000 µg/ml, p< 0.001) Table 1). 4. Discussion Currently, no available therapy whether used alone or in combination can fully restore normal blood glucose homeostasis or prevent long-term complications, and existing antidiabetic drugs still have notable limitations [31]. Crocin has shown a reduction of blood glucose levels in experimental diabetic models [25]. There are numerous studies conducted to evaluate the antidiabetic effects of crocin [32] [33]; however, the detailed mechanism of action of crocin remains unclear. This study aims to investigate the mechanism of action of crocin involving the pathways of insulin secretion and peripheral action by evaluating the effects on carbohydrate digestion and absorption in vivo and in vitro , and DPPH activity. The insulin-stimulating effects of crocin were evaluated using a perfused rat pancreas model. Findings indicate that crocin’s antihyperglycemic activity is partly due to its ability to stimulate insulin secretion from pancreatic β-cells. Upon reintroduction of crocin at 11 mM glucose, a sustained increase in insulin release was observed (P<0.05), suggesting enhanced glucose-stimulated insulin secretion. Non-toxic dose of crocin was used to explore mechanisms underlying the stimulation of insulin secretion in the absence and presence of known modulators of β -cell function. Diazoxide, a K ATP -channel opener [34], inhibited the insulin-releasing effects of crocin. This suggests that crocin closes K ATP channels to induce insulinotropic action. Furthermore, the L-type voltage-dependent Ca 2+ channel blocker, verapamil [34], also reduced the insulin-releasing effects of crocin. This suggests a dependency on the Ca 2+ channel to induce insulin release. Crocin may promote insulin secretion by acting on ATP-sensitive K + channels, similar to sulfonylurea drugs, which bind to sulfonylurea receptors on β-cells, causing K + channel closure, membrane depolarization, and subsequent Ca 2+ influx [34]. IBMX, a Phosphodiesterase (PDE) inhibitor, increases cAMP concentration and potentiates insulin secretion [35]. Crocin did not stimulate insulin release enhanced by IBMX (100 mm), suggesting the insulin secretory effect of crocin is not possibly related to the involvement of other pathways such as the adenylate cyclase/cAMP, rather than depolarization of the cell membrane. Inhibiting α-amylase and α-glucosidase enzymes effectively reduces postprandial hyperglycemia by delaying carbohydrate breakdown and glucose absorption. This gradual glucose release helps regulate glycemic fluctuations and reduces the metabolic burden on pancreatic β-cells following food intake [36]. Acarbose, a well-known α-glucosidase inhibitor, served as the reference standard and almost completely suppressed glucose release from starch [37] [38]. Crocin markedly inhibited glucose absorption both in an in situ perfused rat intestine and during in vitro glucose diffusion over a 6-hour period. This inhibition may stem from crocin’s interference with intestinal glucose transport [39]. Crocin also enhanced gastrointestinal motility as assessed by BaSO₄ milk transit which may contribute to reduced carbohydrate absorption. As expected, co-administration of crocin with sucrose resulted in elevated levels of unabsorbed sucrose in the gut and a corresponding reduction in postprandial blood glucose. Elevated sucrose levels in the gastrointestinal tract reflect impaired digestion and absorption. Consequently, more sucrose reaches the large intestine and caecum, where it is ultimately excreted. Crocin appears to reduce postprandial sucrose absorption and accelerate GI motility, likely by limiting carbohydrate digestion and shortening transit or gastric emptying time. This study observed a concentration-dependent inhibition of glucose release from starch following crocin treatment. The previous study also showed that crocin effectively inhibited α-glucosidase and α-amylase enzymes [40]. Similar to dietary fibers, crocin may reduce GI transit time, thereby limiting the window for carbohydrate digestion and absorption and mitigating postprandial hyperglycemia [34]. Oxidative stress significantly contributes to diabetes and its complications [41], underscoring the protective role of antioxidants in neutralizing free radicals and preventing disease progression. Accordingly, this study assessed crocin’s antioxidant potential through its DPPH radical scavenging activity. These findings align with earlier reports demonstrating crocin’s strong antioxidant properties [42]. 5. Conclusion Crocin significantly stimulates insulin secretion from pancreatic β-cells, likely through membrane depolarization. Both in vivo and in vitro findings demonstrate that crocin reduces gastrointestinal carbohydrate digestion and absorption, enhances gut motility, and exhibits notable antioxidant activity via DPPH inhibition . These multifaceted actions suggest that crocin holds promise as an adjunctive therapy for the management of type 2 diabetes mellitus. Acknowledgements This research was supported by the University Research Fund, Independent University, Bangladesh (IUB). JMA Hannan and Peter R Flatt were responsible for the conception and design of the research and also contributed equally to the supervision of the study. Asma Ahammed performed the experiments. 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Supplementary Material File (figures_crocin.docx) Download 879.96 KB File (table_crocin.docx) Download 15.28 KB Information & Authors Information Version history V1 Version 1 16 May 2025 Copyright This work is licensed under a Non Exclusive No Reuse License. Keywords anti-oxidants diabetes endocrine pharmacology in vivo pharmacokinetics Authors Affiliations Asma Ahammed View all articles by this author Metrics & Citations Metrics Article Usage 410 views 215 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Asma Ahammed. Crocin stimulates insulin secretion via the activation of K+ and Ca2+ channels, and inhibits carbohydrate digestion and absorption, and DPPH. Authorea . 16 May 2025. DOI: https://doi.org/10.22541/au.174737369.98827055/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. 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