Impact of treatment with recombinant human GH and IGF-I on visceral adipose tissue and glucose homeostasis in adults.
Supraphysiological doses of growth hormone (GH) therapy are generally thought to antagonize the effects of insulin, whereas the insulin-like growth factor I (IGF-I) potentiates insulin-like actions. Paradoxically, adults with GH deficiency and patients with acromegaly are both predisposed to glucose intolerance and insulin resistance; however, one cannot extrapolate from these pathological conditions to determine the true metabolic roles of GH and IGF-I in glucose homeostasis. Growth hormone also promotes lipolysis, which has been shown to be the principal determinant of its insulin-antagonistic properties; on the other hand, IGF-I, which acts as an insulin sensitizer, does not exert any direct effect on lipolysis or lipogenesis. Under physiological conditions, the insulin-sensitizing effect of IGF-I is evident only after feeding, when the bioavailability of circulating IGF-I is increased. In contrast to supraphysiological GH doses, low doses of GH treatment have been shown to increase circulating IGF-I levels and IGF-I bioavailability and, thus, may theoretically enhance insulin sensitivity without inducing lipolysis. We have recently reported that a fixed administration of a very low GH dose (1.7 microg/kg/day or 0.1mg/day) improved insulin sensitivity in adults with GH deficiency and increased peripheral glucose uptake in subjects with impaired glucose tolerance and the metabolic syndrome. Our data raise the possibility that this very low GH dose may play a role in maintaining beta-cell function and possibly delay the progression to type 2 diabetes in these high-risk patients.
Yuen
Kevin C J
KC
Division of Endocrinology, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, L607 Portland, OR 97239-3098, USA. yuenk@ohsu.edu
Dunger
David B
DB
D000328:Adult; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000378:metabolism*; D013006:Growth Hormone / Q000008:administration & dosage / Q000172:deficiency / Q000378:metabolism / Q000502:physiology / Q000627:therapeutic use*; D020249:Hormone Replacement Therapy; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000502:physiology / Q000627:therapeutic use*; D050152:Intra-Abdominal Fat / Q000187:drug effects*; D024821:Metabolic Syndrome / Q000188:drug therapy
D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D005947:Glucose