Involvement of insulin-like growth factor-I in the control of glucose homeostasis.
Insulin-like growth factor-I (IGF-I) has significant structural homology with proinsulin. IGF-I binds to insulin receptors, stimulates insulin-like actions and enhances insulin sensitivity. However, because circulating IGF-I is bound to high-affinity binding proteins and has relatively low affinity for insulin receptors, most of its ability to alter insulin sensitivity is mediated indirectly (i.e. through suppression of growth hormone, a known insulin antagonist). Direct effects of IGF-I on insulin actions are tissue specific, occurring principally in skeletal muscle and kidney. Genetic manipulations in experimental mouse models have been used to analyze the role of endogenous IGF-I on insulin action. These studies have shown that suppression of growth hormone is important for enhancing insulin action in the liver and that deletion of the IGF-I receptor in skeletal muscle results in severe insulin resistance. IGF-I also suppresses renal gluconeogenesis, which might contribute to its glucose-lowering actions. In humans, IGF-I enhances insulin sensitivity and lowers blood glucose in patients with either extreme insulin resistance or type 2 diabetes. It also decreases insulin requirement in patients with insulin-deficient diabetes. Taken together, these findings suggest that IGF-I is functioning coordinately with insulin to regulate glucose homeostasis.
Clemmons
David R
DR
CB# 7170, 8024 Burnett-Womack, Division of Endocrinology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7170, USA. endo@med.unc.edu <endo@med.unc.edu>
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000627:therapeutic use; D007333:Insulin Resistance; D007334:Insulin-Like Growth Factor I / Q000627:therapeutic use*
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D007334:Insulin-Like Growth Factor I