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

作者：Chadderdon Scott M^*; Belcik J Todd; Smith Elise; Pranger Lindsay; Kievit Paul; Grove Kevin L; Lindner Jonathan R

来源：American Journal of Physiology - Endocrinology And Metabolism, 2012, 303(5): E607-E613.

DOI：10.1152/ajpendo.00231.2012

• echocardiography
• regional blood flow
• inactivity

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%26apos;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 %26lt; 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 %26lt; 0.01) and exercise (0.10 +/- 0.02 vs. 0.20 +/- 0.02 ml/g, P %26lt; 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.

• 出版日期2012-9