Natural anti-diabetic compound 1,2,3,4,6-penta-O-galloyl-D-glucopyranose binds to insulin receptor and activates insulin-mediated glucose transport signaling pathway.

摘要: Insulin mimetics from natural sources are potential therapeutics that can act alone or supplement insulin and other anti-diabetic drugs in the prevention treatment of diabetes. We recently reported insulin-like glucose transport stimulatory activity tannic acid (TA) 3T3-L1 adipocytes. In this study, we find chemically synthesized 1,2,3,4,6-penta-O-galloyl-beta-D-glucopyranose (beta-PGG), one components TA, as well its anomer alpha-PGG possess activity. Mechanistic studies adipocytes with alpha-PGG, more potent two anomers, reveal inhibitors block insulin-mediated transport, including inhibits receptor (IR), also completely abolish activated by alpha-PGG. addition, induces phosphorylation IR Akt, activates PI 3-kinase, stimulates membrane translocation GLUT 4. Receptor binding indicate binds to affects between reducing maximum without significantly altering affinity IR. Western blotting analysis products a cross-linking reaction suggests may bind at site located on alpha-subunit receptor. Animal demonstrate PGG reduces blood levels improves tolerance diabetic obese animals. Our results suggest serve model for development new types anti-metabolic syndrome therapeutics.