Geniposide protects pancreatic INS-1E β cells from hIAPP-induced cell damage: potential involvement of insulin degrading-enzyme.

Islet amyloid deposition is increasingly seen as a pathogenic feature of type 2 diabetes mellitus (T2DM), with the deposits containing the unique amyloidogenic peptide islet amyloid polypeptide (IAPP, also known as amylin). The fibril precursors of IAPP contribute to its cytotoxicity on pancreatic β cells and be important in causing β-cell dysfunction in T2DM. However, the development of effective this study, inhibitors against the toxicity of IAPP has been extremely challenging. We have found that pre-incubation with geniposide dose-dependently prevented human IAPP (hIAPP)-induced cell damage in INS-1E cells, and bacitracin, an inhibitor of IDE activity, prevented significantly the protective effects of geniposide in pancreatic INS-1E cells significantly. Geniposide induced the expression of insulin-degrading enzyme (IDE), a key degrading protein of hIAPP, but had no significant effect on the aggregation of hIAPP. These findings indicate that geniposide prevents hIAPP-induced cytotoxicity in INS-1E cells involving upregulation of IDE expression.