Epigallocatechin gallate (EGCG) and rutin suppress the glucotoxicity through activating IRS2 and AMPK signaling in rat pancreatic beta cells.
Pancreatic beta cell failure is one critical metabolic disorder in the development of type 2 diabetes. Decreased viability and dysfunction of beta cells would accelerate the diabetic pathogenesis associated with higher mortality. In this study, the tea polyphenol EGCG (epigallocatechin gallate) and the buckwheat flavonoid Rutin were investigated to attenuate the induced glucotoxicity in beta cells. EGCG and Rutin could preserve the insulin secretory machinery and stimulate insulin receptor substrate 2 (IRS2) signaling in rat pancreatic beta cells, RIN-m5F. These findings further demonstrated the reduced glucolipotoxic effects of EGCG and Rutin through activating AMP-activated protein kinase (AMPK) signaling to inhibit the activities of lipogenic enzymes and ameliorating mitochondrial function. Consequently, the cell viability was retained after attenuating the glucotoxicity through the broad effect of EGCG and Rutin. The intrinsic protective effects of EGCG and Rutin in preserving the insulin signaling and regulating lipogenesis, manipulating cell cycling, and maintaining mitochondrial function to achieve the integrity of beta cells, which highlight the possibilities of EGCG and Rutin as novel strategies for the prevention of type 2 diabetes.
Cai
Erica P
EP
Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan 100.
Lin
Jen-Kun
JK
D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D045744:Cell Line, Tumor; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D005947:Glucose / Q000633:toxicity*; D006801:Humans; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D012431:Rutin / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*
D055504:Insulin Receptor Substrate Proteins; D012431:Rutin; D002392:Catechin; C045651:epigallocatechin gallate; D055372:AMP-Activated Protein Kinases; D005947:Glucose