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 μmol · 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 ΔMBV 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.