title: Geniposide protects pancreatic INS-1E β cells from hIAPP-induced cell damage: potential involvement of insulin degrading-enzyme.
abstract: 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.
authors.affiliation: College of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing, 400054, China; Chongqing Key Lab of Catalysis and Functional Organic Molecules, Chongqing Technology and Business University, Chongqing, 400067, China; College of Chemistry and Chemical Engineering, Chongqing University, Chongqing, 400030, China.
authors.forename: Yonglan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Fei
authors.initials: F
authors.lastname: Yin
authors.forename: Jianhui
authors.initials: J
authors.lastname: Liu
authors.forename: Yanwen
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001414:Bacitracin / Q000378:metabolism; D045744:Cell Line, Tumor; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000473:pathology; D006801:Humans; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007339:Insulysin / Q000378:metabolism*; D039823:Iridoids / Q000494:pharmacology*; D058228:Islet Amyloid Polypeptide / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats
chemical_list: D039823:Iridoids; D058228:Islet Amyloid Polypeptide; D020011:Protective Agents; D001414:Bacitracin; C007835:geniposide; D007339:Insulysin
keywords: cytotoxicity; geniposide; human islet amyloid peptide; type 2 diabetes mellitus (T2DM)