2-Deoxyglucose Tissue Levels and Insulin Levels Following Tolazamide Dosing in Normal and Obese Mice

Summary

The effect of tolazamide (TZ), a sulfonylurea, on ¹⁴C-2-deoxyglucose (¹⁴C-2DG) tissue distribution and insulin levels of normal and obese mice was investigated using an in vivo physiological method. Acute doses of TZ (50 mg/kg ip) increased ¹⁴C-2DG levels in gastrocnemius muscle and retroperitoneal fat and produced a transient elevation of insulin which most likely accounts for the increased ¹⁴C-2DG levels in muscle and fat. The results demonstrate that the in vivo ¹⁴C-2DG method produced results consistent with known actions of sulfonylureas on in vitro hexose assimilation in muscle and fat. Subchronic treatment (7 days) with TZ 50 mg/kg ip twice daily did not result in increased insulin-stimulated ¹⁴C-2DG tissue levels in normal mice when compared to saline treated controls. However, insulin levels were lower in mice treated subchronically with TZ compared to saline controls suggesting an enhancement of insulin action. Viable yellow obese mice represent a model of maturity onset obesity presenting with insulin resistance. The insulin resistance of this obese strain appears to reside in the fat tissue as assessed by comparing ¹⁴C-2DG tissue levels of obese mice with lean littermate controls. Subchronic TZ treatment had no effect on ¹⁴C-2DG uptake in fat or muscle tissue of viable yellow obese mice and did not alter their plasma insulin levels. It appears that genetically obese viable yellow mice may be resistant to subchronic treatment with TZ.

Key words

Tolazamide - Viable yellow obese mice - 2-Deoxyglucose - Sulfonylurea