Effect of metformin on blood glucose, insulin and C-peptide responses to glucagon in non-insulin dependent diabetics.

Since the C-peptide Radioimmuno active/Immuno Reactive Insulin (CPR/IRI) molar ratio is considered as an index of insulin hepatic extraction and tissue receptor binding, the AA. investigated the effects of metformin on this index after glucagon infusion in non-insulin dependent diabetics. Fourteen lean subjects (aged 48 to 67 years, mean 54 +/- 7) with non-insulin dependent diabetes were studied. At 9.00 a.m. each subject after overnight fasting, underwent glucagon infusion (1 mg i.v. diluted in 250 ml of saline, infused at a rate of 8.3 gamma/min for 2 hours); blood specimen were obtained at --15, 0, 30, 60, 90, 120 min. This test was repeated after a five-day treatment with metformin (1.5 g per os). For each sample plasma glucose by glucose oxidase method, plasma insulin and C-peptide by Radio Immuno Assay (RIA) method were determined. After treatment with metformin the hyperglycemia induced by glucagon was not influenced; nevertheless insulin and C-peptide plasma levels showed an evident reduction while CPR/IRI molar ratio was unchanged. The AA. suppose an indirect effect of metformin upon beta cells, namely a less pancreatic insulin requirement, mediated by an improvement of glucose utilization.