Effects of acute metabolic interventions on hemodynamics, endothelial function and forearm glucose uptake

Abstract: Hyperinsulinemia is known to augment endothelium-dependent.vasodilation (EDV). If physiological levels of insulin lead to peripheral, vasodilation and if this vasodilation is an independent determinant of skeletal muscle glucose uptake is however under debate. In this thesis the effects of acute metabolic interventions on hemodynamics, endothelial function and forearm glucose uptake were evaluated in healthy subjects. Normoglycemic hyperinsulinemia, as well as ingestion of an ordinary mixed meal, resulted in an increase in forearm blood flow. This increase in flow acted as a late amplifier of insulin mediated limb glucose uptake and contributeed to a substantial part of the total skeletal muscle glucose uptake. In the early events of insulin-mediated glucose uptake, however, an increase in glucose extraction was the main determinant. Acute hyperglycemia, as well as acute hyperlipidemia and ingestion of a mixed meal attenuated endothelium-dependent vasodilation. Endothelium-independent vasodilation was, however, left unaffected. During both hyperglycemia and hyperlipidemia, the attenuation in EDV was normalised by superimposing hyperinsulinemia. The attenuation in EDV after a mixed meal was transient and recovered after 2 hours. The different metabolic interventions induced divergent peripheral and central hemodynamic patterns. Hyperinsulinemia resulted in vasodilation and increased cardiac output similar to that observed after ingestion of a mixed meal. In conclusion, insulin-mediated vasodilation seems to have the ability to amplify insulin-mediated glucose uptake in healthy subjects. All metabolic interventions evaluated, except hyperinsulinemia, resulted in an attenuation of EDV. Hyperinsulinemia, on the other hand, reversed this attenuation. The hemodynamic response seen after ingestion of a mixed meal seems largely to be mediated by hyperinsulinemia.