Hyperglycaemia but not hyperlipidaemia causes beta cell dysfunction and beta cell loss in the domestic cat
| Autor: | Melania Osto, Aurel Perren, Eric Zini, Thomas A. Lutz, Philippe Linscheid, Marco Franchini, Claudia E Reusch, M Bouwman, R S Heller, Mathias Ackermann, Marc Y. Donath, Franco Guscetti |
|---|---|
| Přispěvatelé: | University of Zurich, Zini, Eric |
| Rok vydání: | 2008 |
| Předmět: |
Blood Glucose
Male medicine.medical_specialty Programmed cell death 10253 Department of Small Animals Endocrinology Diabetes and Metabolism 10184 Institute of Veterinary Pathology Hyperlipidemias 610 Medicine & health Fatty Acids Nonesterified Biology Cat Diseases Insulin resistance In vivo Insulin-Secreting Cells Internal medicine Diabetes mellitus Internal Medicine medicine Animals Insulin Beta (finance) 10081 Institute of Veterinary Physiology medicine.disease 2712 Endocrinology Diabetes and Metabolism Endocrinology 2724 Internal Medicine Apoptosis Animals Domestic Hyperglycemia Toxicity Cats 570 Life sciences biology Beta cell 10244 Institute of Virology |
| Zdroj: | Zini, E.; Osto, M.; Franchini, M.; Guscetti, F.; Donath, M. Y.; Perren, Aurel; 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), pp. 336-346. Springer 10.1007/s00125-008-1201-y |
| ISSN: | 1432-0428 0012-186X |
| DOI: | 10.1007/s00125-008-1201-y |
| Popis: | 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 |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink