Vascular dysfunction and insulin stimulated blood flow : impact of physical inactivity and type 2 diabetes

Abstract

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Individuals with type 2 diabetes (T2D) have blunted femoral artery insulin mediated blood flow which is critical for the delivery and uptake of glucose into skeletal muscle. However, it is unclear in humans the precise mechanisms by which insulin resistance impairs insulin stimulated blood flow. Further, chronic physical inactivity is a powerful stimulus for reduced insulin sensitivity and vascular dysfunction; however, the effects of short term, modest reductions in physical activity are limited. Thus, we examined 1) if inactivity for 5 days would impair endothelial function in healthy individuals (study one) 2) if reducing whole body insulin sensitivity, via 5 days of inactivity, would impair the blood flow response to insulin stimulation in parallel with glycemic control (study two) and 3) phosphorylation of endothelial nitric oxide (eNOS) and endothelin-1 (ET-1) production to insulin stimulation would be decreased and increased, respectively, in insulin resistant individuals (study three). We demonstrated significant reductions in endothelial function with only 5 days of reduced daily steps while blood flow to glucose ingestion was unaltered. Further, in obese humans with type 2 diabetes it does not appear that that the reduction in blood flow to 1 hr of insulin stimulation is due to altered peNOS or ET-1. Collectively, these data suggest that reduced daily physical activity and chronic insulin resistance mediate negative impacts on vascular function and insulin stimulated blood flow and signaling.