Pharmacological Antilipolysis Restores Insulin Sensitivity During Growth Hormone Exposure

• Published in: Diabetes (New York, N.Y.) Vol. 50; no. 10; pp. 2301 - 2308
• Main Authors: NIELSEN, Steen, MØLLER, Niels, CHRISTIANSEN, Jens S, JØRGENSEN, Jens O. L
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.10.2001
• Subjects: Adult; Adults; Biological and medical sciences; Diabetes; Diabetes research; Diabetes. Impaired glucose tolerance; Drug Therapy, Combination; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Energy Metabolism; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Fatty acids; Female; Glucose; Glucose - metabolism; Growth Hormone - deficiency; Growth Hormone - therapeutic use; Growth hormones; Hormones - blood; Humans; Hyperinsulinism - metabolism; Hypolipidemic Agents - therapeutic use; Insulin - physiology; Insulin resistance; Lipid Metabolism; Lipolysis; Lipolysis - drug effects; Male; Medical sciences; Metabolism; Metabolites; Middle Aged; Oxidation; Physiological aspects; Pyrazines - therapeutic use; Random Allocation; Somatotropin; Denmark; Endocrinopathy; Human; Pancreatic hormone; Sensitivity resistance; Diabetes mellitus; Somatotropin hormone; Glucose; Metabolism; Insulin; Lipolysis
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/diabetes.50.10.2301

Pharmacological Antilipolysis Restores Insulin Sensitivity During Growth Hormone Exposure Steen Nielsen , Niels Møller , Jens S. Christiansen and Jens O.L. Jørgensen Medical Department M, Aarhus University Hospital, DK-8000 Aarhus C, Denmark Abstract Stimulation of lipolysis and the induction of resistance to insulin’s actions on glucose metabolism are well-recognized effects of growth hormone (GH). To evaluate whether these two features are causally linked, we studied the impact of pharmacologically induced antilipolysis in seven GH-deficient patients (mean [± SE] age 37 ± 4 years). Each subject was studied under four different conditions: during continuation of GH replacement alone (A), after discontinuation of GH replacement for 2 days (B), after GH replacement and short-term coadministration of acipimox (250 mg, p.o., b.i.d., for 2 days) (C), and after administration of acipimox alone (D). At the end of each study, total and regional substrate metabolisms were assessed in the basal state and after a 3-h hyperinsulinemic/euglycemic clamp. Serum levels of free fatty acids (FFAs) were elevated with GH alone (A) and suppressed with acipimox (C and D). Basal rates of lipid oxidation were highest with GH alone (A), and suppressed by 50% with acipimox (B versus D, P < 0.01; A versus C, P < 0.05). Basal glucose oxidation rates were lowest with GH alone (A) and highest with acipimox (C and D) ( P = 0.01). Insulin-stimulated rates of total glucose turnover were significantly lower with GH alone as compared with all other conditions ( P = 0.004). Insulin sensitivity as assessed by the M value (rate of glucose infusion) was reduced with GH alone as compared with all other conditions ( M value in mg · kg −1 · min −1 : GH alone [A], 2.55 ± 0.64; discontinuation of GH [B], 4.01 ± 0.70; GH plus acipimox [C], 3.96 ± 1.34; acipimox alone [D], 4.96 ± 0.91; P < 0.01). During pharmacological antilipolysis, GH did not significantly influence insulin sensitivity (C versus D; P = 0.19). From our results, we reached the following conclusions: 1 ) Our data strongly suggest that the insulin antagonistic actions of GH on glucose metabolism are causally linked to the concomitant activation of lipolysis. 2 ) In addition, GH may induce residual insulin resistance through non–FFA-dependent mechanisms. 3 ) The cellular and molecular mechanisms subserving the insulin antagonistic effects of GH remain to be elucidated. Footnotes Address correspondence and reprint requests to Jens Otto Lunde Jørgensen, M.D., Medical Department M, Aarhus University Hospital, DK-8000 Aarhus C, Denmark. E-mail: jolj{at}dadlnet.dk . Received for publication 25 October 2000 and accepted in revised form 26 June 2001. ANOVA, analysis of variance; AUC, area under the curve; EE, energy expenditure; FFA, free fatty acid; GH, growth hormone; GLM, general linear model; M value, rate of glucose infusion; R a , rate of appearance; R d , rate of disappearance.