Is lactate involved in phenformin-induced insulin secretion?

Phenformin at high doses (10 mg/l, 50 mg/l, and 100 mg/l) increased the insulin and lactate output rates by the isolated perfused rat pancreas. Glucagon secretion was not modified. There was a statistically significant correlation between the increase in insulin and lactate output rates induced by phenformin. Intra-pancreatic L (+) lactate concentrations induced by phenformin were in the range of sodium L (+) lactate concentrations which experimentally stimulated insulin secretion by the same preparation. Thiamin pyrophosphate and sodium dichloroacetate, which promote the aerobic metabolism of pyruvate, opposed the phenoformin induced increase in lactate output by the isolated perfused rat pancreas and provoked as well a decrease in insulin release. These results suggest that the increase in insulin secretion following the administration of phenformin at high concentrations can be explained, to a large extent, by the increase in the production of lactate ions.