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

BackgroundIn the present study, the possible anti-diabetic action of biguanide and thiazolidinediones administered supraspinally or spinally was studied in ICR mice.MethodsMice 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.ResultsWe 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.ConclusionsOur 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.

► I.c.v. with metformin or rosiglitazone slightly attenuated the blood glucose level.
► I.c.v. or i.t. with metformin attenuated the blood glucose level in STZ model.
► Metformin and rosiglitazone appear to be mediated via the brain regions.
► I.c.v. or i.t. with metformin may be effective for treating IDDM.