Therapeutic aspects of growth hormone and insulin-like growth factor-I treatment on visceral fat and insulin sensitivity in adults.
Growth hormone (GH) is generally considered to exert anti-insulin actions, whereas insulin-like growth factor I (IGF-I) has insulin-like properties. Paradoxically, GH deficient adults and those with acromegaly are both predisposed to insulin resistance, but one cannot extrapolate from these pathological conditions to determine the normal metabolic roles of GH and IGF-I on glucose homeostasis. High doses of GH treatment have major effects on lipolysis, which plays a crucial role in promoting its anti-insulin effects, whereas IGF-I acts as an insulin sensitizer that does not exert any direct effect on lipolysis or lipogenesis. Under physiological conditions, the insulin-sensitizing effect of IGF-I is only evident after feeding when the bioavailability of circulating IGF-I is increased. In contrast, many studies in GH deficient adults have consistently shown that GH replacement improves the body composition profile although these studies differ considerably in terms of age, the presence or absence of multiple pituitary hormone deficiency, and whether GH deficiency was childhood or adult-onset. However, the improvement in body composition does not necessarily translate into improvements in insulin sensitivity presumably due to the anti-insulin effects of high doses of GH therapy. More recently, we have found that a very low dose GH therapy (0.1 mg/day) improved insulin sensitivity without affecting body composition in GH-deficient adults and in subjects with metabolic syndrome, and we postulate that these effects are mediated by its ability to increase free 'bioavailable' IGF-I without the induction of lipolysis. These results raise the possibility that this low GH dose may play a role in preventing the decline of beta-cell function and the development of type 2 diabetes in these "high risk" subjects.
Yuen
K C J
KC
Division of Endocrinology, Oregon Health and Science University, Portland, Oregon, USA. yuenk@ohsu.edu
Dunger
D B
DB
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D013006:Growth Hormone / Q000627:therapeutic use*; D019382:Human Growth Hormone / Q000172:deficiency; D006801:Humans; D007333:Insulin Resistance; D007334:Insulin-Like Growth Factor I / Q000627:therapeutic use*; D050152:Intra-Abdominal Fat / Q000187:drug effects*; D024821:Metabolic Syndrome / Q000188:drug therapy* / Q000378:metabolism
D001786:Blood Glucose; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone