Activity restriction, impaired capillary function, and the development of insulin resistance in lean primates

Chadderdon SM, Belcik JT, Smith E, Pranger L, Kievit P, Grove KL, Lindner JR. Activity restriction, impaired capillary function, and the development of insulin resistance in lean primates. Am J Physiol Endocrinol Metab 303: E607-E613, 2012. First published June 26, 2012; doi:10.1152/ajpendo.00231.2012.-Insulin produces capillary recruitment in skeletal muscle through a nitric oxide (NO)-dependent mechanism. Capillary recruitment is blunted in obese and diabetic subjects and contributes to impaired glucose uptake. This study's objective was to define whether inactivity, in the absence of obesity, leads to impaired capillary recruitment and contributes to insulin resistance (IR). A comprehensive metabolic and vascular assessment was performed on 19 adult male rhesus macaques (Macaca mulatta) after sedation with ketamine and during maintenance anesthesia with isoflurane. Thirteen normal-activity (NA) and six activity-restricted (AR) primates underwent contrast-enhanced ultrasound to determine skeletal muscle capillary blood volume (CBV) during an intravenous glucose tolerance test (IVGTT) and during contractile exercise. NO bioactivity was assessed by flow-mediated vasodilation. Although there were no differences in weight, basal glucose, basal insulin, or truncal fat, AR primates were insulin resistant compared with NA primates during an IVGTT (2,225 +/- 734 vs. 5,171 +/- 3,431 mu g.ml(-1).min(-1), P < 0.05). Peak CBV was lower in AR compared with NA primates during IVGTT (0.06 +/- 0.01 vs. 0.12 +/- 0.02 ml/g, P < 0.01) and exercise (0.10 +/- 0.02 vs. 0.20 +/- 0.02 ml/g, P < 0.01), resulting in a lower peak skeletal muscle blood flow in both circumstances. The insulin-mediated changes in CBV correlated inversely with the degree of IR and directly with activity. Flow-mediated dilation was lower in the AR primates (4.6 +/- 1.0 vs. 9.8 +/- 2.3%, P = 0.01). Thus, activity restriction produces impaired skeletal muscle capillary recruitment during a carbohydrate challenge and contributes to IR in the absence of obesity. Reduced NO bioactivity may be a pathological link between inactivity and impaired capillary function.