title: Obesity blunts insulin-mediated microvascular recruitment in human forearm muscle.
abstract: We have previously shown that skeletal muscle capillaries are rapidly recruited by physiological doses of insulin in both humans and animals. This facilitates glucose and insulin delivery to muscle, thus augmenting glucose uptake. In obese rats, both insulin-mediated microvascular recruitment and glucose uptake are diminished; however, this action of insulin has not been studied in obese humans. Here we used contrast ultrasound to measure microvascular blood volume (MBV) (an index of microvascular recruitment) in the forearm flexor muscles of lean and obese adults before and after a 120-min euglycemic-hyperinsulinemic (1 mU . min(-1) . kg(-1)) clamp. We also measured brachial artery flow, fasting lipid profile, and anthropomorphic variables. Fasting plasma glucose (5.4 +/- 0.1 vs. 5.1 +/- 0.1 mmol/l, P = 0.05), insulin (79 +/- 11 vs. 38 +/- 6 pmol/l, P = 0.003), and percent body fat (44 +/- 2 vs. 25 +/- 2%, P = 0.001) were higher in the obese than the lean adults. After 2 h of insulin infusion, whole-body glucose infusion rate was significantly lower in the obese versus lean group (19.3 +/- 3.2 and 37.4 +/- 2.6 mumol . min(-1) . kg(-1) respectively, P < 0.001). Compared with baseline, insulin increased MBV in the lean (18.7 +/- 3.3 to 25.0 +/- 4.1, P = 0.019) but not in the obese group (20.4 +/- 3.6 to 18.8 +/- 3.8, NS). Insulin increased brachial artery diameter and flow in the lean but not in the obese group. We observed a significant, negative correlation between DeltaMBV and BMI (R = -0.482, P = 0.027) in response to insulin. In conclusion, obesity eliminated the insulin-stimulated muscle microvascular recruitment and increased brachial artery blood flow seen in lean individuals.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Virginia Health System, P.O. Box 801410, 450 Ray C. Hunt Drive, Charlottesville, VA 22908, USA.
authors.forename: Lucy H
authors.initials: LH
authors.lastname: Clerk
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Vincent
authors.forename: Linda A
authors.initials: LA
authors.lastname: Jahn
authors.forename: Zhenqi
authors.initials: Z
authors.lastname: Liu
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Lindner
authors.forename: Eugene J
authors.initials: EJ
authors.lastname: Barrett
mesh_terms: D000328:Adult; D001783:Blood Flow Velocity / Q000187:drug effects / Q000502:physiology*; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D001916:Brachial Artery / Q000000981:diagnostic imaging / Q000503:physiopathology*; D005542:Forearm / Q000098:blood supply*; D015309:Glucose Clamp Technique; D006801:Humans; D007328:Insulin / Q000097:blood / Q000494:pharmacology; D007700:Kinetics; D008055:Lipids / Q000097:blood; D008833:Microcirculation / Q000502:physiology*; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000187:drug effects / Q000503:physiopathology*; D009765:Obesity / Q000097:blood / Q000503:physiopathology*; D012016:Reference Values; D014463:Ultrasonography
chemical_list: D001786:Blood Glucose; D007328:Insulin; D008055:Lipids