Insulin action in muscle and adipose tissue in type 2 diabetes: The significance of blood flow

Under normal metabolic conditions insulin stimulates microvascular perfusion (capillary recruitment) of skeletal muscle and subcutaneous adipose tissue and thus increases blood flow mainly after meal ingestion or physical exercise. This helps the delivery of insulin itself but also that of substrates and of other signalling molecules to multiple tissues beds and facilitates glucose disposal and lipid kinetics. This effect is impaired in insulin resistance and type 2 diabetes early in the development of metabolic dysregulation and reflects early-onset endothelial dysfunction. Failure of insulin to increase muscle and adipose tissue blood flow results in decreased glucose handling. In fat depots, a blunted postprandial blood flow response will result in an insufficient suppression of lipolysis and an increased spill over of fatty acids in the circulation, leading to a more pronounced insulin resistant state in skeletal muscle. This defect in blood flow response is apparent even in the prediabetic state, implying that it is a facet of insulin resistance and exists long before overt hyperglycaemia develops. The following review intends to summarize the contribution of blood flow impairment to the development of the atherogenic dysglycemia and dyslipidaemia.