title: Drosophila melanogaster as a model system for studies of islet amyloid polypeptide aggregation.
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.
  
  
  RESULTS
  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 elav(C155,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, both known to detect amyloid. Also, the morphology of the highly organized protein granules that developed in the fat body of the head in hIAPP and hproIAPP expressing flies was characterized, and determined to consist of 15.8 nm thick pentagonal rod-like structures.
  
  
  CONCLUSIONS
  These findings point to a potential for Drosophila melanogaster to serve as a model system for studies of hproIAPP and hIAPP expression with subsequent aggregation and developed pathology.
authors.affiliation: Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Sebastian Wolfgang
authors.initials: SW
authors.lastname: Schultz
authors.forename: K Peter R
authors.initials: KP
authors.lastname: Nilsson
authors.forename: Gunilla Torstensdotter
authors.initials: GT
authors.lastname: Westermark
mesh_terms: D000595:Amino Acid Sequence; D000682:Amyloid / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified; D003224:Congo Red / Q000378:metabolism; D004331:Drosophila melanogaster / Q000166:cytology / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D005110:Extracellular Space / Q000378:metabolism; D005216:Fat Body / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D058228:Islet Amyloid Polypeptide / Q000737:chemistry* / Q000378:metabolism; D051379:Mice; D023421:Models, Animal; D008969:Molecular Sequence Data; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D020836:Protein Structure, Quaternary; D016019:Survival Analysis; D013876:Thiophenes / Q000378:metabolism; D019076:Transgenes / Q000235:genetics
chemical_list: D000682:Amyloid; D058228:Islet Amyloid Polypeptide; D013876:Thiophenes; C422904:pro-islet amyloid polypeptide; D003224:Congo Red