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Graded occlusion of perfused rat muscle vasculature decreases insulin action


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Vollus, GC, Bradley, EA, Roberts, MK, Newman, JMB, Richards, SM, Rattigan, S, Barrett, EJ and Clark, MG 2007 , 'Graded occlusion of perfused rat muscle vasculature decreases insulin action' , Clinical Science, vol. 112, no. 8 , pp. 457-466 , doi: 10.1042/CS20060311.

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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 Thr172 (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−1 · g−1 of wet weight) rat hindlimb led to increased pressure (−0.5+−0.8, 15.9+−
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
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.

Item Type: Article
Authors/Creators:Vollus, GC and Bradley, EA and Roberts, MK and Newman, JMB and Richards, SM and Rattigan, S and Barrett, EJ and Clark, MG
Keywords: blood flow, capillary, glucose uptake, insulin, muscle oxygen uptake, restricted nutritive capacity, skeletal muscle. Abbreviations: 5-HT, 5-hydroxytryptamine; AMPK, AMP-activated protein kinase; AngII, angiotensin II; Cr, creatine; EC, energy charge; HRP, horseradish peroxidase; MS, microspheres; P-Akt, Akt phosphorylated on Ser473; P-AMPK, AMPK phosphorylated on Thr172; PCr, phosphocreatine; ˙Vo2, oxygen uptake.
Journal or Publication Title: Clinical Science
Publisher: Portland Press
ISSN: 0143-5221
DOI / ID Number: 10.1042/CS20060311
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