Central anti-diabetic action of biguanide and thizolidinediones in D-glucose fed and streptozotocin-treated mouse models.

Background: In the present study, the possible anti-diabetic action of biguanide and thiazolidinediones administered supraspinally or spinally was studied in ICR mice.

Methods: Mice were intracerebroventricular (i.c.v.) or intrathecal (i.t.) treated with 20 or 30 μg metformin, pioglitazone and rosiglitazone in d-glucose fed and streptozotocin-treated models, and blood glucose levels was measured at 30, 60 and 120 min after i.c.v. or i.t. administration.

Results: We found that i.c.v. injection with metformin or rosiglitazone slightly attenuated the blood glucose level in d-glucose fed model, whereas pioglitazone showed no effect on the blood glucose level in d-glucose fed model. The i.t. administration with metformin, pioglitazone or rosiglitazone did not alter the blood glucose level in d-glucose fed model. We also assessed the possible roles of biguanide and thiazolidinedione in the regulation of the blood glucose level in streptozotocin-treated model. We found in the present study that i.c.v. or i.t. administration with metformin caused a pronounced attenuation of the blood glucose level in streptozotocin-treated model. However, rosiglitazone administered i.c.v. did not affect the blood glucose level in streptozotocin-treated model.

Conclusions: Our results suggest that the anti-diabetic actions of metformin and rosiglitazone appear to be mediated via the brain regions as revealed in d-glucose fed animal model. Furthermore, metformin administered supraspinally or spinally may be effective for treating type I diabetes mellitus as revealed in streptozotocin-treated mouse model.