EFFECTS OF METFORMIN ON GLUCOSE UPTAKE BY ISOLATED DIAPHRAGM FROM NORMAL AND DIABETIC RATS

The effects of the antidiabetic drug metformin (Nl, Nl-dimethylbiguanide) on glucose uptake by isolated rat diaphragm muscle have been studied. A therapeutic concentration of metformin (10 μg/ml) had no effect on glucose uptake by diaphragm muscle from normal rats incubated in the absence or presence of insulin (100 and 1000 μU/ml), but increased uptake by diaphragm muscle from alloxan-diabetic rats incubated in the presence of insulin (P < 0.05). Diaphragm muscle from normal rats incubated in a medium containing sodium butyrate (0.25 mg/ml) showed a reduction in glucose uptake similar to that seen in muscle from diabetic animals. Metformin (10 μg/ml) also increased glucose uptake by this preparation in the presence of insulin (P < 0.01). A higher concentration of metformin (100 μg/ml) caused a depression of glucose uptake by diaphragms from normal rats, and the necessity for studying therapeutic concentrations of the biguanide drugs is stressed. The relation of these findings to the antidiabetic effect of the drug in man is discussed. The mechanisms involved are discussed in terms of changes in glycogen metabolism. © 1972