Gymnemic Acid Ameliorates Pancreatic β-Cell Dysfunction by Modulating Pdx1 Expression: A Possible Strategy for β-Cell Regeneration

BACKGROUND: Endogenous pancreatic beta-cell regeneration is a promising therapeutic approach for enhancing beta-cell function and neogenesis in diabetes. Various findings have reported that regeneration might occur via stimulating beta-cell proliferation, neogenesis, or conversion from other pancreatic cells to beta-like cells. Although the current scenario illustrates numerous therapeutic strategies and approaches that concern endogenous beta-cell regeneration, all of them have not been successful to a greater extent because of cost effectiveness, availability of suitable donors and rejection in case of transplantation, or lack of scientific evidence for many phytochemicals derived from plants that have been employed in traditional medicine. Therefore, the present study aims to investigate the effect of gymnemic acid (GA) on beta-cell regeneration in streptozotocin-induced type 1 diabetic rats and high glucose exposed RIN5-F cells. METHODS: The study involves histopathological and immunohistochemical analysis to examine the islet's architecture. Quantitative polymerase chain reaction (qPCR) and/or immunoblot were employed to quantify the beta-cell regeneration markers and cell cycle proliferative markers. RESULTS: The immunoexpression of E-cadherin, P-catenin, and phosphoinositide 3-kinases/protein kinase B were significantly increased in GA-treated diabetic rats. On the other hand, treatment with GA upregulated the pancreatic regenerative transcription factor viz. pancreatic duodenal homeobox 1, Neurogenin 3, MafA, NeuroD1, and beta-cells proliferative markers such as CDK4, and Cyclin D1, with a simultaneous downregulation of the forkhead box O, glycogen synthase kinase-3, and p21(cip1) in diabetic treated rats. Adding to this, we noticed increased nuclear localization of Pdxl in GA treated high glucose exposed RIN5-F cells. CONCLUSION: Our results suggested that GA acts as a potential therapeutic candidate for endogenous beta-cell regeneration in treating type 1 diabetes. [GRAPHICS] .

Automated summary

Gymnemic acid (GA) may serve as a potential therapeutic candidate for endogenous beta-cell regeneration in treating type 1 diabetes.