Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Development of diabetes in obese, insulin-resistant mice: Essential role of dietary carbohydrate in beta cell destruction.
Diabetologia 50, 1481-1489 (2007)
AIMS/HYPOTHESIS: The role of dietary carbohydrate in the pathogenesis of type 2 diabetes is still a subject of controversial debate. Here we analysed the effects of diets with and without carbohydrate on obesity, insulin resistance and development of beta cell failure in the obese, diabetes-prone New Zealand Obese (NZO) mouse. MATERIALS AND METHODS: NZO mice were kept on a standard diet (4% [w/w] fat, 51% carbohydrate, 19% protein), a high-fat diet (15, 47 and 17%, respectively) and a carbohydrate-free diet in which carbohydrate was exchanged for fat (68 and 20%, respectively). Body composition and blood glucose were measured over a period of 22 weeks. Glucose tolerance tests and euglycaemic-hyperinsulinaemic clamps were performed to analyse insulin sensitivity. Islet morphology was assessed by immunohistochemistry. RESULTS: Mice on carbohydrate-containing standard or high-fat diets developed severe diabetes (blood glucose >16.6 mmol/l, glucosuria) due to selective destruction of pancreatic beta cells associated with severe loss of immunoreactivity of insulin, glucose transporter 2 (GLUT2) and musculoaponeurotic fibrosarcoma oncogene homologue A (MafA). In contrast, mice on the carbohydrate-free diet remained normoglycaemic and exhibited hyperplastic islets in spite of a morbid obesity associated with severe insulin resistance and a massive accumulation of macrophages in adipose tissue. CONCLUSIONS/INTERPRETATION: These data indicate that the combination of obesity, insulin resistance and the inflammatory response of adipose tissue are insufficient to cause beta cell destruction in the absence of dietary carbohydrate.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
ISSN (print) / ISBN
0012-186X
e-ISSN
1432-0428
Zeitschrift
Diabetologia
Quellenangaben
Band: 50,
Heft: 7,
Seiten: 1481-1489
Verlag
Springer
Verlagsort
Berlin ; Heidelberg [u.a.]
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Diabetes and Obesity (IDO)