Prevention of nutritionally induced diabetes by rosiglitazone in the gerbil Psammomys obesus.

BACKGROUND

Psammomys obesus is a desert gerbil developing hyperglycaemia, hyperinsulinaemia and insulin resistance when placed for 2 weeks on a high-energy (HE) diet. The mechanism underlying the antidiabetic effect of rosiglitazone (RG) treatment (20 mg/kg per day for 2 weeks) was studied.

METHODS

The antidiabetogenic effect of RG treatment on serum insulin and metabolic parameters in serum and target tissues of insulin action was investigated in vivo and compared with the pancreatic beta cell protective effects of RG.

RESULTS

Almost all RG-treated animals remained normoglycaemic compared to controls, but, at the same time, they were hyperinsulinaemic. RG had no effect on serum free fatty acid and serum and muscle triglyceride concentrations and did not appreciably affect body weight and fat depots. RG prevented a HE diet-induced reduction of GLUT 4 glucose transporter content in epididymal adipose tissue, but not in gastrocnemius muscle. The normoglycaemic effect was not associated with a suppression of liver PEPCK activity. Muscle PKCepsilon expression, known to be elevated in diabetic Psammomys and to inhibit insulin signalling, was only marginally decreased. However, RG treatment prevented the marked decrease in insulin immunostaining as well as the vacuolization of the beta cells and accelerated beta cell proliferation.

CONCLUSIONS

These data indicate that the skeletal muscle is not the primary target of RG action, whereas the preservation of the insulin secretory capacity and the prevention of degenerative beta cell vacuolization in spite of persisting insulin resistance appear to be the basis for the anti-hyperglycaemic effect of RG in Psammomys.