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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-8833

Zini, E; Osto, M; Franchini, M; Guscetti, F; Donath, M Y; Perren, A; Heller, R S; Linscheid, P; Bouwman, M; Ackermann, M; Lutz, T A; Reusch, C E (2009). Hyperglycaemia but not hyperlipidaemia causes beta cell dysfunction and beta cell loss in the domestic cat. Diabetologia, 52(2):336-346.

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Abstract

AIMS/HYPOTHESIS: 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/INTERPRETATION: 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.

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35 citations in Web of Science®
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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:05 Vetsuisse Faculty > Institute of Veterinary Physiology
05 Vetsuisse Faculty > Institute of Veterinary Pathology
05 Vetsuisse Faculty > Institute of Virology
05 Vetsuisse Faculty > Veterinary Clinic > Department of Small Animals
DDC:570 Life sciences; biology
Language:English
Date:February 2009
Deposited On:18 Dec 2008 14:07
Last Modified:30 Oct 2014 15:51
Publisher:Springer
ISSN:0012-186X
Publisher DOI:10.1007/s00125-008-1201-y
PubMed ID:19034421

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