Effects of growth hormone on glucose, lipid, and protein metabolism in human subjects.
In evolutionary terms, GH and intracellular STAT 5 signaling is a very old regulatory system. Whereas insulin dominates periprandially, GH may be viewed as the primary anabolic hormone during stress and fasting. GH exerts anabolic effects directly and through stimulation of IGF-I, insulin, and free fatty acids (FFA). When subjects are well nourished, the GH-induced stimulation of IGF-I and insulin is important for anabolic storage and growth of lean body mass (LBM), adipose tissue, and glycogen reserves. During fasting and other catabolic states, GH predominantly stimulates the release and oxidation of FFA, which leads to decreased glucose and protein oxidation and preservation of LBM and glycogen stores. The most prominent metabolic effect of GH is a marked increase in lipolysis and FFA levels. In the basal state, the effects of GH on protein metabolism are modest and include increased protein synthesis and decreased breakdown at the whole body level and in muscle together with decreased amino acid degradation/oxidation and decreased hepatic urea formation. During fasting and stress, the effects of GH on protein metabolism become more pronounced; lack of GH during fasting increases protein loss and urea production rates by approximately 50%, with a similar increase in muscle protein breakdown. GH is a counterregulatory hormone that antagonizes the hepatic and peripheral effects of insulin on glucose metabolism via mechanisms involving the concomitant increase in FFA flux and uptake. This ability of GH to induce insulin resistance is significant for the defense against hypoglycemia, for the development of "stress" diabetes during fasting and inflammatory illness, and perhaps for the "Dawn" phenomenon (the increase in insulin requirements in the early morning hours). Adult patients with GH deficiency are insulin resistant-probably related to increased adiposity, reduced LBM, and impaired physical performance-which temporarily worsens when GH treatment is initiated. Conversely, despite increased LBM and decreased fat mass, patients with acromegaly are consistently insulin resistant and become more sensitive after appropriate treatment.
Møller
Niels
N
Medical Department M, Aarhus University Hospital, Aarhus Sygehus, DK, Aarhus, Denmak.
Jørgensen
Jens Otto Lunde
JO
D000172:Acromegaly / Q000209:etiology / Q000628:therapy; D003920:Diabetes Mellitus / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006130:Growth Disorders / Q000188:drug therapy; D020249:Hormone Replacement Therapy / Q000009:adverse effects; D019382:Human Growth Hormone / Q000172:deficiency / Q000494:pharmacology*; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D050356:Lipid Metabolism / Q000187:drug effects*; D008954:Models, Biological; D011506:Proteins / Q000378:metabolism*; D035842:Research Subjects
D011506:Proteins; D019382:Human Growth Hormone; D005947:Glucose