Recombinant human insulin-like growth factor-I: a therapeutic challenge for diabetes mellitus.
Insulin-like growth factor I (IGF I) is an endocrine hormone that mediates most of the effects of pituitary growth hormone. Other important regulatory factors of serum IGF I levels are insulin and nutrition. Most of the circulating IGF I is bound to three IGF binding proteins (BP), mostly IGFBP-3, BP-2 and BP-1. IGF I is also produced by many cells in the body where it exerts autocrine and/or paracrine effects. IGF I has a specific receptor on most cells, the so-called type 1 IGF receptor. When IGF I is administered intravenously as a bolus it leads to acute hypoglycaemia in a similar way to insulin and mainly with the insulin receptor. Chronic administration of IGF I to hypophysectomized or diabetic rats leads to prominent anabolic effects and growth. In this manuscript, metabolic and endocrine effects of recombinant IGF I are discussed. Recombinant IGF I therapy increases energy expenditure and lipid oxidation and decreases proteolysis and protein oxidation. These effects occur despite a partial inhibition of insulin and growth hormone secretion. The therapeutic spectrum of recombinant IGF I, consisting of inhibition of catabolism, stimulation of anabolism, decreases of triglyceride and cholesterol levels and a striking increase in insulin sensitivity, renders IGF I a very interesting, powerful tool for insulin-resistant states such as non-insulin-dependent diabetes mellitus.
Froesch
E R
ER
Department of Internal Medicine, University of Zurich, Switzerland.
Hussain
M
M
D000818:Animals; D001363:Awards and Prizes; D001786:Blood Glucose / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000188:drug therapy* / Q000266:history; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy; D005060:Europe; D005947:Glucose / Q000378:metabolism; D049673:History, 20th Century; D006801:Humans; D007016:Hypophysectomy; D007328:Insulin / Q000502:physiology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology / Q000502:physiology / Q000627:therapeutic use*; D008055:Lipids / Q000097:blood; D008954:Models, Biological; D017526:Receptor, IGF Type 1 / Q000502:physiology; D011994:Recombinant Proteins / Q000627:therapeutic use; D012016:Reference Values; D012955:Societies, Medical; D013557:Switzerland
D001786:Blood Glucose; D007328:Insulin; D008055:Lipids; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; D005947:Glucose