title: Metformin potentiates the antigluconeogenic action of insulin.
abstract: The interaction of metformin and insulin in the control of hepatic gluconeogenesis was examined in isolated hepatocytes from 48h starved rats using lactate (10(-2) mol/l) with pyruvate (10(-3) mol/l) as substrate. During 1 h incubations in the absence of added insulin, 10(-2) and 10(-3) mol/l metformin reduced gluconeogenesis by 65% and 59% respectively, but lower concentrations of metformin were not effective. Insulin alone (10(-6)-10(-8) mol/l) reduced (37%-16%) gluconeogenesis. The effect of insulin was enhanced (further reductions of 11%-24%) by 5 x 10(-4) mol/l metformin, although this concentration of metformin was not effective in the absence of insulin. At lower insulin concentrations (10(-9) and 10(-10) mol/l) which did not significantly affect gluconeogenesis alone, 5 x 10(-4) mol/l metformin decreased gluconeogenesis (32% and 28% respectively). At 10(-10) mol/l insulin, metformin concentrations of 10(-3)-10(-7) mol/l decreased gluconeogenesis by 60-20%. The results suggest that therapeutic concentrations of metformin may act synergistically with physiological concentrations of insulin to suppress hepatic gluconeogenesis.
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004357:Drug Synergism; D005943:Gluconeogenesis / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology*; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D008687:Metformin / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D007328:Insulin; D008687:Metformin; D005947:Glucose