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Hyperglycaemia but not hyperlipidaemia causes beta cell dysfunction and beta cell loss in the domestic cat

Zini, E. ; Osto, M. ; Franchini, M. ; Guscetti, F. ; Donath, M. ; Perren, A. ; Heller, R. ; Linscheid, P. ; Bouwman, M. ; Ackermann, M. ; Lutz, T. ; Reusch, C.

In: Diabetologia, 2009, vol. 52, no. 2, p. 336-346

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    Titel
    • Hyperglycaemia but not hyperlipidaemia causes beta cell dysfunction and beta cell loss in the domestic cat
    Autor
    • Zini, E.. Clinic for Small Animal Internal Medicine, Vetsuisse Faculty, University of Zürich, Winterthurerstrasse 260, 8057, Zurich, Switzerland
    • Osto, M.. Institute of Veterinary Physiology, Vetsuisse Faculty, University of Zürich, Zurich, Switzerland
    • Franchini, M.. Institute of Virology, Vetsuisse Faculty, University of Zürich, Zurich, Switzerland
    • Guscetti, F.. Institute of Veterinary Pathology, Vetsuisse Faculty, University of Zürich, Zurich, Switzerland
    • Donath, M.. Division of Endocrinology and Diabetes and Center for Integrated Human Physiology, University Hospital of Zürich, Zurich, Switzerland
    • Perren, A.. Department of Pathology, Technische Universität München, Klinikum Rechts der Isar, Munich, Germany
    • Heller, R.. Department of Developmental Biology, Hagedorn Research Institute, Gentofte, Denmark
    • Linscheid, P.. Clinic for Small Animal Internal Medicine, Vetsuisse Faculty, University of Zürich, Winterthurerstrasse 260, 8057, Zurich, Switzerland
    • Bouwman, M.. Department of Clinical Sciences of Companion Animals, Utrecht University, Utrecht, The Netherlands
    • Ackermann, M.. Institute of Virology, Vetsuisse Faculty, University of Zürich, Zurich, Switzerland
    • Lutz, T.. Institute of Veterinary Physiology, Vetsuisse Faculty, University of Zürich, Zurich, Switzerland
    • Reusch, C.. Clinic for Small Animal Internal Medicine, Vetsuisse Faculty, University of Zürich, Winterthurerstrasse 260, 8057, Zurich, Switzerland
    Dokumententyp
    • Postprint
    OAI-PMH-ID
    • oai:doc.rero.ch:309885
    Summary
    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 10days to clamp their blood concentrations at the approximate level found in untreated feline diabetes (glucose: 25-30mmol/l; triacylglycerols: 3-7mmol/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 2days 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