Metformin Normalizes Insulin Binding to Monocytes from Obese Nondiabetic Subjects and Obese Type II Diabetic Patients

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Abstract
In order to evaluate the in vivo effects of biguanides on the insulin receptor, we have studied insulin binding to circulating monocytes of six normal controls, eight obese nondiabetic subjects, and six obese type II diabetic patients, both before and after 4 days of treatment with the biguanide metformin (850 mg twice daily orally). Before drug administration, 125I-insulin binding to monocytes was decreased in obese subjects and diabetic patients. After metformin administration, an increase in insulin binding to peripheral monocytes was observed in seven of eight obese nondiabetic subjects (3.57 ± 0.43 to 4.69 ± 0.59% bound at 107 monocytes, mean ± sem, P < 0.01) and in all diabetic patients (3.21 ± 0.21 to 5.22 ± 0.34, P < 0.01). Scatchard plots indicated that the increased binding was due to an increase in the receptor number. In contrast, no significant change in insulin binding was found in normal controls after metformin administration (5.31 ± 0.14 and 4.70 ± 0.12). These studies indicate that metformin normalizes the binding of insulin to its receptor in obese subjects and diabetic patients. It is suggested, therefore, that the action of metformin on the insulin receptor may be one of the mechanisms of the antidiabetic effect of this drug.

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