Relevance of the vascular effects of insulin in the rationale of its therapeutical use.
Beyond carbohydrate, lipid and protein metabolism, insulin influences hemostasis, vascular tone and angiogenesis. Insulin per se causes a slow-acting vasodilation selectively occurring in skeletal muscle tissue, mainly related to an endothelium-dependent mechanism. Insulin-induced vasodilation is attenuated by the secretion of endothelin-1 and by the stimulation of sympathetic activity. The direct vasodilating effect of insulin is deeply reduced in the insulin-resistant states. The insulin effects on platelet aggregation and inflammatory response are attributable to increased synthesis of nitric oxide, and are deeply reduced in the insulin-resistant states. Furthermore, insulin reduces oxidative stress and promotes angiogenesis and proliferation of vascular smooth muscle cells. The involvement of insulin signalling pathways in these different insulin actions both in insulin sensitive and in insulin resistant states and the concept of "selective insulin resistance" are discussed. The vascular effects of insulin are generally ignored in the clinical practice, despite the evidences that insulin infusion with algorithms aiming to provide an optimal blood glucose control improves the clinical outcomes of patients with severe acute illness and myocardial infarction. Aim of this review is to clarify whether the vascular effects of insulin could represent a new "rationale" for its therapeutical use, independently of the well known metabolic actions.
Anfossi
Giovanni
G
Department of Clinical and Biological Sciences of the Turin University, San Luigi Gonzaga Hospital, I-10043 Orbassano (Turin), Italy. giovanni.anfossi@unito.it
Russo
Isabella
I
Doronzo
Gabriella
G
Trovati
Mariella
M
D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000150:complications; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007328:Insulin / Q000494:pharmacology* / Q000627:therapeutic use; D007333:Insulin Resistance / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction
D007004:Hypoglycemic Agents; D007328:Insulin