Grant: CIHR/Regional Partnership Program/Operating Grants

Hormones released in response to a meal result in rapid glucose uptake into skeletal muscle. This response includes dilation of blood vessels in skeletal muscle that allows increased delivery of glucose to the muscle. We have recently discovered that the selective uptake of glucose into skeletal muscle is dependent upon a hormone released from the liver in response to insulin. Insulin administered to healthy rats results in vasodilation of the skeletal muscle only in situations where the hepatic hormone is released. The vasodilation is actually caused by this hormone and not insulin. In this study, rats will be made diabetic by providing them with free access to a high sugar drink. The health of the blood vessels will be assessed at several stages during the development of the disease and the ability of insulin to cause vasodilation secondary to release of the hepatic hormone will be determined. The ability of drugs that have been shown to restore the release of the hepatic hormone to also restore the vasodilator response to insulin will be assessed. This work relates directly to the numerous vascular dysfunctions known to be associated with diabetes and result in hypertension, blindness, cardiac and kidney toxicity, and often result in limb amputations.