title: Combining short-term metformin treatment and one bout of exercise does not increase insulin action in insulin-resistant individuals.
abstract: Results from the Diabetes Prevention Program highlight the effectiveness of metformin or regular physical activity in the prevention of type 2 diabetes. Independently, metformin and exercise increase insulin sensitivity, but they have not been studied in combination. To assess the combined effects, insulin-resistant subjects (n = 9) matched for weight, body fat, and aerobic fitness were studied before any treatment (B), after 2-3 wk of 2,000 mg/day metformin (MET), and after metformin plus 40 min of exercise at 65% Vo(2peak) (MET + Ex). A second group (n = 7) was studied at baseline and after an identical bout of exercise with no metformin (Ex). Biopsies of the vastus lateralis were taken at B, after MET, immediately after MET + Ex (group 1), or immediately after Ex (group 2). Insulin sensitivity was assessed 4 h postexercise with a euglycemic hyperinsulinemic (40 mU.m(2).min(-1)) clamp enriched with [6,6-(2)H]glucose. Insulin sensitivity was 54% higher after Ex (P < 0.01), but there was no change with Met + Ex. Skeletal muscle AMPKalpha2 activity was elevated threefold (P < 0.01) after Ex, but there was no increase with MET + Ex. These findings suggest that the combination of short-term metformin treatment and an acute bout of exercise does not enhance insulin sensitivity, and the addition of metformin may attenuate the well-documented effects of exercise alone.
authors.affiliation: Department of Kinesiology, University of Massachusetts Amherst, USA.
authors.forename: Carrie G
authors.initials: CG
authors.lastname: Sharoff
authors.forename: Todd A
authors.initials: TA
authors.lastname: Hagobian
authors.forename: Steven K
authors.initials: SK
authors.lastname: Malin
authors.forename: Stuart R
authors.initials: SR
authors.lastname: Chipkin
authors.forename: Haiyan
authors.initials: H
authors.lastname: Yu
authors.forename: Michael F
authors.initials: MF
authors.lastname: Hirshman
authors.forename: Laurie J
authors.initials: LJ
authors.lastname: Goodyear
authors.forename: Barry
authors.initials: B
authors.lastname: Braun
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000328:Adult; D015153:Blotting, Western; D015444:Exercise / Q000502:physiology*; D005260:Female; D015309:Glucose Clamp Technique; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology* / Q000502:physiology*; D007333:Insulin Resistance / Q000502:physiology*; D019344:Lactic Acid / Q000097:blood; D008297:Male; D008687:Metformin / Q000494:pharmacology*; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D010766:Phosphorylation
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D019344:Lactic Acid; D008687:Metformin; C534978:Prkaa2 protein, mouse; D055372:AMP-Activated Protein Kinases