A feline model of experimentally induced islet amyloidosis

The study of the pathogenesis of islet amyloidosis and its relationship to the development and progression of type 2 diabetes mellitus has been hamper ed by the lack of an experimentally inducible animal model. The domestic ca t, by virtue of the fact that it is one of the few species that spontaneous ly develop a form of diabetes mellitus that closely resembles human type 2 diabetes, including the formation of amyloid deposits derived from islet am yloid polypeptide (IAPP), was considered to be an excellent candidate speci es in which to attempt to develop a nontransgenic animal model for this dis ease process. To develop the model, 8 healthy domestic cats were given a 50 % pancreatectomy, which was followed by treatment with growth hormone and d examethasone. Once a stable diabetic state was established, cats were rando mly assigned to groups treated with either glipizide or insulin at doses ap propriate to control hyperglycemia. Cats were maintained on this treatment regimen for 18 months and then euthanized. Based on light microscopic exami nation of Congo red-stained sections of pancreas, all cats were negative fo r the presence of islet amyloid at the time of pancreatectomy. At the end o f the study all 4 glipizide-treated cats had islet amyloid deposits, wherea s only 1 of 4 insulin-treated cats had detectable amyloid. In addition, the glipizide treated cats had threefold higher basal and fivefold higher gluc ose-stimulated plasma IAPP concentrations than insulin-treated cats, sugges ting an association between elevated IAPP secretion and islet amyloidosis. Blood-glycosylated hemoglobin concentrations were not significantly differe nt between the two treatment groups. This study documents for the first tim e all inducible model of islet amyloidosis in a nontransgenic animal.