TY - JOUR

T1 - Increased skeletal muscle capillarization enhances insulin sensitivity

AU - Åkerström, Thorbjörn

AU - Laub, Lasse

AU - Vedel, Kenneth

AU - Brand, Christian Lehn

AU - Pedersen, Bente Klarlund

AU - Kaufmann Lindqvist, Anna

AU - Wojtaszewski, Jørgen

AU - Hellsten, Ylva

N1 - CURIS 2014 NEXS 368

PY - 2014

Y1 - 2014

N2 - Increased skeletal muscle capillarization is associated with improved glucose tolerance and insulin sensitivity. However, a possible causal relationship has not previously been identified. We therefore investigated whether increased skeletal muscle capillarization increases insulin sensitivity. Skeletal muscle specific angiogenesis was induced by adding the α1-adrenergic receptor antagonist Prazosin to the drinking water of Sprague Dawley rats (n=33) while 34 rats served as controls. Insulin sensitivity was measured ≥40 h after termination of the 3-week Prazosin treatment, which ensured that Prazosin was cleared from the blood stream. Whole-body insulin sensitivity was measured in conscious, unrestrained rats by hyperinsulinemic euglycemic clamp. Tissue specific insulin sensitivity was assessed by administration of 2-deoxy-[(3)H]-Glucose during the plateau phase of the clamp. Whole-body insulin sensitivity increased by ~24% and insulin-stimulated skeletal muscle 2-deoxy-[(3)H]-Glucose disposal increased by ~30% concomitant with a ~20% increase in skeletal muscle capillarization. Adipose tissue insulin sensitivity was not affected by the treatment. Insulin-stimulated muscle glucose uptake was enhanced independent of improvements in skeletal muscle insulin signaling to glucose uptake and glycogen synthesis, suggesting that the improvement in insulin-stimulated muscle glucose uptake could be due to improved diffusion conditions for glucose in the muscle. The Prazosin treatment did not affect the rats on any other parameters measured. We conclude that an increase in skeletal muscle capillarization is associated with increased insulin sensitivity. These data point towards the importance of increasing skeletal muscle capillarization for prevention or treatment of type 2 diabetes.

AB - Increased skeletal muscle capillarization is associated with improved glucose tolerance and insulin sensitivity. However, a possible causal relationship has not previously been identified. We therefore investigated whether increased skeletal muscle capillarization increases insulin sensitivity. Skeletal muscle specific angiogenesis was induced by adding the α1-adrenergic receptor antagonist Prazosin to the drinking water of Sprague Dawley rats (n=33) while 34 rats served as controls. Insulin sensitivity was measured ≥40 h after termination of the 3-week Prazosin treatment, which ensured that Prazosin was cleared from the blood stream. Whole-body insulin sensitivity was measured in conscious, unrestrained rats by hyperinsulinemic euglycemic clamp. Tissue specific insulin sensitivity was assessed by administration of 2-deoxy-[(3)H]-Glucose during the plateau phase of the clamp. Whole-body insulin sensitivity increased by ~24% and insulin-stimulated skeletal muscle 2-deoxy-[(3)H]-Glucose disposal increased by ~30% concomitant with a ~20% increase in skeletal muscle capillarization. Adipose tissue insulin sensitivity was not affected by the treatment. Insulin-stimulated muscle glucose uptake was enhanced independent of improvements in skeletal muscle insulin signaling to glucose uptake and glycogen synthesis, suggesting that the improvement in insulin-stimulated muscle glucose uptake could be due to improved diffusion conditions for glucose in the muscle. The Prazosin treatment did not affect the rats on any other parameters measured. We conclude that an increase in skeletal muscle capillarization is associated with increased insulin sensitivity. These data point towards the importance of increasing skeletal muscle capillarization for prevention or treatment of type 2 diabetes.

U2 - 10.1152/ajpendo.00020.2014

DO - 10.1152/ajpendo.00020.2014

M3 - Journal article

C2 - 25352432

VL - 307

SP - E1105-E1116

JO - American Journal of Physiology - Endocrinology and Metabolism

JF - American Journal of Physiology - Endocrinology and Metabolism

SN - 0193-1849

IS - 12

ER -