Abstract
1 Type 2 diabetes (T2D) is characterized by impaired glucose uptake in skeletal muscle and adipose tissues, which contributes to systemic hyperglycemia. GLUT4 is a crucial component in insulin-stimulated glucose uptake and its expression as well as translocation are impaired in T2D onset. This study explored the role of extracellular vesicles (EVs) derived from GLUT4-overexpressing engineered muscle constructs (G4OE-EMC) in glucose metabolism. G4OE-EMC-derived EVs enhanced glucose uptake and insulin sensitivity both in vitro, when tested on wild-type (WT) engineered muscle constructs, and in vivo using the diet-induced obesity (DIO) mouse model. Proteomic and transcriptomic analyses revealed that the EVs were enriched in IGF1 and contained reduced levels of miRNAs, such as miR-122-5p, miR-16-5p, and miR-486-5p, which target IGF1R. The multi-omic approach used here suggests a mechanism whereby G4OE-EMC-derived EVs enhance glucose metabolism via IGF1 signaling and miRNA-mediated regulation of IGF1R expression, offering a potential therapeutic strategy for T2D.
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1 Abstract
Type 2 diabetes (T2D) is characterized by impaired glucose uptake in skeletal muscle and adipose tissues, which contributes to systemic hyperglycemia. GLUT4 is a crucial component in insulin-stimulated glucose uptake and its expression as well as translocation are impaired in T2D onset. This study explored the role of extracellular vesicles (EVs) derived from GLUT4-overexpressing engineered muscle constructs (G4OE-EMC) in glucose metabolism. G4OE-EMC-derived EVs enhanced glucose uptake and insulin sensitivity both in vitro, when tested on wild-type (WT) engineered muscle constructs, and in vivo using the diet-induced obesity (DIO) mouse model. Proteomic and transcriptomic analyses revealed that the EVs were enriched in IGF1 and contained reduced levels of miRNAs, such as miR-122-5p, miR-16-5p, and miR-486-5p, which target IGF1R. The multi-omic approach used here suggests a mechanism whereby G4OE-EMC-derived EVs enhance glucose metabolism via IGF1 signaling and miRNA-mediated regulation of IGF1R expression, offering a potential therapeutic strategy for T2D.
Competing Interest Statement
Conflict of interests: S.L ,Y.H.B and H.S are inventors on a patent pending approval (TECH-P-0265-PCT)
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