title: Hyperglycaemia but not hyperlipidaemia causes beta cell dysfunction and beta cell loss in the domestic cat.
abstract: OBJECTIVE
  In vitro studies point to a toxic effect of high glucose and non-esterified fatty acids on beta cells. Whether elevated levels of glucose and lipids induce beta cell loss in vivo is less clear. The domestic cat has recently been proposed as a valuable animal model for human type 2 diabetes because feline diabetes shows several similarities with diabetes in humans, including obesity-induced insulin resistance, impaired beta cell function, decreased number of beta cells and pancreatic amyloid deposition.
  
  
  METHODS
  We infused healthy cats with glucose or lipids for 10 days to clamp their blood concentrations at the approximate level found in untreated feline diabetes (glucose: 25-30 mmol/l; triacylglycerols: 3-7 mmol/l).
  
  
  RESULTS
  Glucose and lipid levels were adequately targeted. Plasma non-esterified fatty acids were increased by lipid infusion 1.7-fold. A dramatic and progressive decline of plasma insulin levels was observed in glucose-infused cats beginning after 2 days of hyperglycaemic clamp. In contrast, plasma insulin concentration and glucose tolerance test were not affected by hyperlipidaemia. Compared with controls, glucose-infused cats had a 50% decrease in beta cells per pancreatic area. Apoptotic islet cells and cleaved caspase-3-positive beta cells were observed in glucose-infused cats only.
  
  
  CONCLUSIONS
  Sustained hyperglycaemia but not hyperlipidaemia induces early and severe beta cell dysfunction in cats, and excess glucose causes beta cell loss via apoptosis in vivo. Hyperglycaemic clamps in cats may provide a good model to study the pathogenesis of glucose toxicity in beta cells.
authors.affiliation: Clinic for Small Animal Internal Medicine, Vetsuisse Faculty, University of Zürich, Winterthurerstrasse 260, 8057 Zurich, Switzerland. ezini@vetclinics.uzh.ch
authors.forename: E
authors.initials: E
authors.lastname: Zini
authors.forename: M
authors.initials: M
authors.lastname: Osto
authors.forename: M
authors.initials: M
authors.lastname: Franchini
authors.forename: F
authors.initials: F
authors.lastname: Guscetti
authors.forename: M Y
authors.initials: MY
authors.lastname: Donath
authors.forename: A
authors.initials: A
authors.lastname: Perren
authors.forename: R S
authors.initials: RS
authors.lastname: Heller
authors.forename: P
authors.initials: P
authors.lastname: Linscheid
authors.forename: M
authors.initials: M
authors.lastname: Bouwman
authors.forename: M
authors.initials: M
authors.lastname: Ackermann
authors.forename: T A
authors.initials: TA
authors.lastname: Lutz
authors.forename: C E
authors.initials: CE
authors.lastname: Reusch
mesh_terms: D000818:Animals; D000829:Animals, Domestic; D001786:Blood Glucose / Q000378:metabolism; D002371:Cat Diseases / Q000503:physiopathology*; D002415:Cats; D005230:Fatty Acids, Nonesterified / Q000097:blood / Q000633:toxicity; D006943:Hyperglycemia / Q000503:physiopathology / Q000662:veterinary*; D006949:Hyperlipidemias / Q000503:physiopathology / Q000662:veterinary*; D007328:Insulin / Q000097:blood; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D008297:Male
chemical_list: D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin