Graded occlusion of perfused rat muscle vasculature decreases insulin action
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Vollus, GC and Bradley, EA and Roberts, NK and Newman, JMB and Richards, SM and Rattigan, S and Barrett, EJ and Clark, MG, Graded occlusion of perfused rat muscle vasculature decreases insulin action, Clinical Science, 112, (8) pp. 457-466. ISSN 0143-5221 (2007) [Refereed Article]
Insulin increases capillary recruitment in vivo and impairment of this may contribute to muscle insulin resistance by limiting either insulin or glucose delivery. In the present study, the effect of progressively decreased rat muscle perfusion on insulin action using graded occlusion with MS (microspheres; 15 μm in diameter) was examined. EC (energy charge), PCr/Cr (phosphocreatine/ creatine ratio), AMPK (AMP-activated protein kinase) phosphorylation on Thr 172 (P-AMPKα/total AMPK), oxygen uptake, nutritive capacity, 2-deoxyglucose uptake, Akt phosphorylation on Ser473 (P-Akt/total Akt) and muscle 2-deoxyglucose uptake were determined. Arterial injection of MS (0, 9, 15 and 30 × 106 MS/15 g of hindlimb muscle, as a bolus) into the pump-perfused (0.5 ml·min-1g-1 of wet weight) rat hindlimb led to increased pressure (-0.5 ± 0.8, 15.9 ± 2.1, 28.7 ± 4.6 and 60.3 ± 9.4 mmHg respectively) with minimal changes in oxygen uptake. Nutritive capacity was decreased from 10.6 ± 1.0 to 3.8 ± 0.9 μmol·g-1 of muscle·h -1 (P < 0.05) with 30 × 106 MS. EC was unchanged, but PCr/Cr was decreased dose-dependently to 61 % of basal with 30 × 106 MS. Insulin-mediated increases in P-Akt/total Akt decreased from 2.15 ± 0.35 to 1.41 ± 0.23 (P < 0.05) and muscle 2-deoxyglucose uptake decreased from 130 ± 19 to 80 ± 12 μg·min -1·g-1 of dry weight (P < 0.05) with 15 × 106 MS; basal P-AMPKα in the absence of insulin was increased, but basal P-Akt/total Akt and muscle 2-deoxyglucose uptake were unaffected. In conclusion, partial occlusion of the hindlimb muscle has no effect on basal glucose uptake and marginally impacts on oxygen uptake, but markedly impairs insulin delivery to muscle and, thus, insulin-mediated Akt phosphorylation and glucose uptake. © 2007 The Biochemical Society.
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