The effects of metformin on adipocyte insulin action and metabolic control in obese subjects with type 2 diabetes.
To investigate the mechanisms of action of metformin, insulin receptor binding and the activity of several insulin-controlled metabolic pathways were measured in adipocytes taken from 10 obese Type 2 diabetic patients treated for 4 weeks with either metformin (0.5 g x 3 daily) or matching placebo using a double-blind crossover design. Metformin therapy was associated with a significant fall in serum fructosamine levels (3.1 +/- 0.4 vs 2.8 +/- 0.4 mmol l-1, p less than 0.02) as well as fasting (10.8 +/- 2.4 vs 9.4 +/- 2.1 mmol l-1) and daytime (11.5 +/- 2.4 vs 10.0 +/- 2.2 mmol l-1) plasma glucose concentrations (p less than 0.05). Fasting and postprandial plasma levels of C-peptide and insulin were unchanged. While fasting plasma lactate concentrations remained unaltered after metformin, a rise was noted in response to meals (from 1.4 +/- 0.1 to 1.8 +/- 0.2 mmol l-1, p less than 0.05). Adipocyte insulin receptor binding was unaffected by drug treatment. Moreover, no insulin-like effects or post-binding potentiation of insulin action could be found on adipocyte glucose transport, glucose oxidation, lipogenesis, glycolysis or antilipolysis. A complementary in vitro study using adipocytes from non-obese healthy volunteers failed to show any direct effect of metformin on adipocyte insulin binding or glucose transport and metabolism, at media drug concentrations corresponding to therapeutic plasma levels.
Pedersen
O
O
Division of Endocrinology and Metabolism, University Clinics of Internal Medicine, Aarhus Amtssygehus, Denmark.
Nielsen
O
O
Bak
J
J
Richelsen
B
B
Beck-Nielsen
H
H
Sørensen
N
N
D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism; D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D003920:Diabetes Mellitus / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007328:Insulin / Q000502:physiology*; D008297:Male; D008687:Metformin / Q000494:pharmacology*; D008875:Middle Aged; D009765:Obesity; D011972:Receptor, Insulin / Q000187:drug effects
D001786:Blood Glucose; D007328:Insulin; D008687:Metformin; D011972:Receptor, Insulin