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.

Diabetologia. 2007 Apr 17;
Development of diabetes in obese, insulin-resistant mice: essential role of
dietary carbohydrate in beta cell destruction.

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.

PMID: 17437079

hth
Gys