(+)-Catechin mitigates impairment in insulin secretion and beta cell damage in methylglyoxal-induced pancreatic beta cells.

ABSTRACT

BACKGROUND: The formation of advanced glycation end products (AGEs) is the central process contributing to diabetic complications in diabetic individuals with sustained and inconsistent hyperglycemia. Methylglyoxal, a reactive carbonyl species, is found to be a major precursor of AGEs, and its levels are elevated in diabetic conditions. Dysfunction of pancreatic beta cells and impairment in insulin secretion are the hallmarks of diabetic progression. Exposure to methylglyoxal-induced AGEs alters the function and maintenance of pancreatic beta cells. Hence, trapping methylglyoxal could be an ideal approach to alleviate AGE formation and its influence on beta cell proliferation and insulin secretion, thereby curbing the progression of diabetes to its complications. METHODS AND RESULTS: In the present study, we have explored the mechanism of action of (+)-Catechin against methylglyoxal-induced disruption in pancreatic beta cells via molecular biology techniques, mainly western blot. Methylglyoxal treatment decreased insulin synthesis (41.5%) via downregulating the glucose-stimulated insulin secretion pathway (GSIS). This was restored upon co-treatment with (+)-Catechin (29.9%) in methylglyoxal-induced Beta-TC-6 cells. Also, methylglyoxal treatment affected the autocrine function of insulin by disrupting the IRS1/PI3k/Akt pathway. Methylglyoxal treatment suppresses Pdx-1 and Maf A levels, which are responsible for beta cell maintenance and cell proliferation. (+)-Catechin could significantly augment the levels of these transcription factors. CONCLUSION: This is the first study to examine the impact of a natural compound on methylglyoxal with the insulin-mediated autocrine and paracrine activities of pancreatic beta cells. The results indicate that (+)-Catechin exerts a protective effect against methylglyoxal exposure in pancreatic beta cells and can be considered a potential anti-glycation agent in further investigations on ameliorating diabetic complications.