Role of insulin and proinsulin in diabetic vascular disease.
Associations between loss of glucose tolerance, insulin resistance, and ischemic heart disease (IHD) are of great current concern. Considerable controversy and uncertainty relates to the mechanism(s) that underlies these associations. Whilst there is some evidence in prospective studies of an association between hyperinsulinemia and future IHD, it is by no means strong or consistent between different studies. Hypertriglyceridemia is another possible factor involved in the linkage between glucose intolerance and IHD. There is good evidence for an affect of plasma nonesterified fatty acids (NEFA) to increase hepatic output of VLDL. Insulin, contrary to some suggestions, acts to lower plasma VLDL by actions directly on hepatic output and activation of adipose tissue lipoprotein lipase, and indirectly via the hormones affect of lowering plasma NEFA. Glycosylation and oxidation of lipoproteins may enhance their atherogenic potential. It is highly probable that procoagulant changes are also important processes predisposing to IHD. Associations between plasminogen activator inhibitor-1 and insulin, intact and 32,33 split proinsulin hypertriglyceridemia, and insulin resistance have been reported, but a unifying hypothesis explaining these links remains elusive. Epidemiological studies now repeated in a number of centers have shown links between infant mortality and birth weight and risk of IHD, and between birth weight and risk of impaired glucose tolerance and non-insulin-dependent diabetes mellitus (NIDDM). It has been proposed, therefore, that impairment of fetal and infant growth may underlie the associations between loss of glucose tolerance and risk of IHD. Animal models form the basis of much current research to test this concept.
D003925:Diabetic Angiopathies / Q000453:epidemiology / Q000209:etiology*; D006801:Humans; D007328:Insulin / Q000502:physiology*; D007333:Insulin Resistance; D008954:Models, Biological; D011384:Proinsulin / Q000502:physiology*
D007328:Insulin; D011384:Proinsulin