Effects of human growth hormone on insulin-stimulated glucose metabolism in 3T3-F442A adipocytes.
GH is believed to play a role in promoting insulin resistance in patients with diabetes and with GH excess. The means by which GH produces insulin resistance may be through direct suppression of glucose metabolism in target cells (insulin-independent) or by interfering with the ability of insulin to stimulate glucose metabolism (insulin-dependent). In 3T3-F442A adipocytes, long term incubation (24-72 h) with GH directly inhibits glucose oxidation and lipid synthesis in the absence of insulin. To distinguish the insulin-independent effects of GH on glucose metabolism from the insulin-dependent effects of GH, we examined the effect of GH on insulin-stimulated lipid accumulation in cultured 3T3-F442A adipocytes. Cells were incubated for 48-72 h with GH and then treated with insulin. Insulin stimulated lipid accumulation in GH-pretreated and control cells. Compared to control, GH-treated cells had lower absolute levels of lipid accumulation in the absence of insulin and at each insulin concentration tested. Thus, GH directly suppresses basal lipid accumulation and lowers the response to insulin. In addition, a 10 times higher insulin concentration was required to reach maximum stimulation of lipid accumulation in GH-treated cells (50 ng/ml) than in control cells (5 ng/ml). When cells were exposed simultaneously to insulin and GH for 72 h, GH treatment inhibited the ability of insulin to stimulate lipid accumulation, and the degree of suppression by GH was related to the GH concentration present. These observations suggest that GH suppresses glucose metabolism not only in the absence but also in the presence of insulin. Since short term (4-h) incubation with GH increases glucose metabolism transiently in GH-deficient preparations, we also examined the influence of short term incubation with GH on insulin responses. Cells were incubated for 4 h with varying concentrations of insulin in the simultaneous presence or absence of GH. Insulin stimulated the conversion of glucose to lipid when tested alone or in the presence of GH. Short term exposure to GH alone also stimulated glucose metabolism. The stimulation of lipid accumulation at insulin concentrations less than 5 ng/ml was greater with GH, but responses were comparable above 5 ng/ml insulin. The ability of insulin to bind to its receptor was not affected by prior treatment with GH for either short or prolonged time periods.(ABSTRACT TRUNCATED AT 400 WORDS)
Foster
C M
CM
Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, Ann Arbor 48109.
Hale
P M
PM
Jing
H W
HW
Schwartz
J
J
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D005947:Glucose / Q000378:metabolism*; D013006:Growth Hormone / Q000494:pharmacology*; D006801:Humans; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology*; D008055:Lipids / Q000096:biosynthesis; D051379:Mice; D010084:Oxidation-Reduction; D011994:Recombinant Proteins
D007328:Insulin; D008055:Lipids; D011994:Recombinant Proteins; D013006:Growth Hormone; D005947:Glucose