The Pattern of Growth Hormone Delivery to Peripheral Tissues Determines Insulin-Like Growth Factor-1 and Lipolytic Responses in Obese Subjects
Open Access
- 1 August 2009
- journal article
- other
- Published by The Endocrine Society in Journal of Clinical Endocrinology & Metabolism
- Vol. 94 (8), 2828-2834
- https://doi.org/10.1210/jc.2009-0638
Abstract
Context: It is unclear whether the pattern of GH delivery to peripheral tissues has important effects. Objective: The aim of the study was to compare the effects of pulsatile vs. continuous administration of GH upon metabolic and IGF-I parameters in obese subjects. Setting: The study was conducted at the General Clinical Research Center at the University of Michigan Medical Center. Participants: Four men and five women with abdominal obesity (body mass index, 33 ± 3 kg/m2; body fat, 40 ± 3%) participated in the study. Intervention: GH (0.5 mg/m2 · d) was given iv for 3 d as: 1) continuous infusion (C); and 2) pulsatile boluses (P) (15% of the dose at 0700, 1300, and 1800 h and 55% at 2400 h). These trials were preceded by a basal period (B) when subjects received normal saline. Main Outcome Measures: Rate of lipolysis and hepatic glucose production were evaluated using stable isotope tracer techniques. The composite index of insulin sensitivity (Matsuda index) was assessed using oral glucose tolerance test. Results: The increase in plasma IGF-I concentrations was greater (P < 0.05) with continuous GH infusion (211 ± 31, 423 ± 38, and 309 ± 34 μg/liter for B, C, and P, respectively). Muscle IGF-I mRNA was significantly increased (P < 0.05) only after the continuous GH infusion (1.2 ± 0.4, 4.4 ± 1.3, and 2.3 ± 0.6 arbitrary units, for B, C, and P, respectively). Only pulsatile GH augmented the rate of lipolysis (4.1 ± 0.3, 4.8 ± 0.7, and 7.1 ± 1.1 μmol/kg · min for B, C, and P, respectively). GH had no effect on hepatic glucose production, but both modes of GH administration were equally effective in impairing insulin sensitivity. Conclusion: These findings indicate that, in obese subjects, discrete components of GH secretory pattern may differentially affect IGF-I generation and lipolytic responses.Keywords
This publication has 37 references indexed in Scilit:
- Role of Growth Hormone in Regulating Lipolysis, Proteolysis, and Hepatic Glucose Production during FastingJournal of Clinical Endocrinology & Metabolism, 2008
- Sex differences in thrombosis in mice are mediated by sex-specific growth hormone secretion patternsJCI Insight, 2008
- Effect of GH on human skeletal muscle lipid metabolism in GH deficiencyAmerican Journal of Physiology-Endocrinology and Metabolism, 2008
- Contribution of Gluconeogenesis and Glycogenolysis to Hepatic Glucose Production in Acromegaly before and after Pituitary MicrosurgeryHormone and Metabolic Research, 2008
- Role of STAT5a in regulation of sex-specific gene expression in female but not male mouse liver revealed by microarray analysisPhysiological Genomics, 2007
- Therapeutic aspects of growth hormone and insulin‐like growth factor‐I treatment on visceral fat and insulin sensitivity in adultsDiabetes, Obesity and Metabolism, 2006
- Alterations in carbohydrate metabolism in response to short-term dietary carbohydrate restrictionAmerican Journal of Physiology-Endocrinology and Metabolism, 2005
- Pulsatility of growth hormone (GH) signalling in liver cells: Role of the JAK-STAT5b pathway in GH actionGrowth Hormone & IGF Research, 2000
- Regulatory mechanisms of growth hormone secretion are sexually dimorphic.JCI Insight, 1998
- Somatotropin antagonism of insulin‐stimulated glucose utilization in 3T3‐L1 adipocytesJournal of Cellular Biochemistry, 1988