drosophila melanogaster as a model system for studies of islet amyloid polypeptide aggregation黑腹果蝇作为模式系统研究胰岛淀粉样多肽聚合.pdfVIP

Drosophila Melanogaster as a Model System for Studies of Islet Amyloid Polypeptide Aggregation 1 2 3 Sebastian Wolfgang Schultz , K. Peter R. Nilsson , Gunilla Torstensdotter Westermark * ¨ ¨ ¨ ¨ 1 Department of Clinical and Experimental Medicine, Linkoping University, Linkoping, Sweden, 2 IFM-Department of Chemistry, Linkoping University, Linkoping, Sweden, 3 Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden Abstract Background: Recent research supports that aggregation of islet amyloid polypeptide (IAPP) leads to cell death and this makes islet amyloid a plausible cause for the reduction of beta cell mass, demonstrated in patients with type 2 diabetes. IAPP is produced by the beta cells as a prohormone, and proIAPP is processed into IAPP by the prohormone convertases PC1/3 and PC2 in the secretory granules. Little is known about the pathogenesis for islet amyloid and which intracellular mechanisms are involved in amyloidogenesis and induction of cell death. Methodology/Principal Findings: We have established expression of human proIAPP (hproIAPP), human IAPP (hIAPP) and the non-amyloidogenic mouse IAPP (mIAPP) in Drosophila melanogaster, and compared survival of flies with the expression driven to different cell populations. Only flies expressing hproIAPP in neurons driven by the Gal4 driver elavC155,Gal4 showed a reduction in lifespan whereas neither expression of hIAPP or mIAPP influenced survival. Both hIAPP and hproIAPP expression caused formation of aggregates in CNS and fat body region, and these aggregates were both stained by the dyes Congo red and pFTAA, bo