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- Title
The pattern of growth hormone delivery to peripheral tissues determines insulin-like growth factor-1 and lipolytic responses in obese subjects.
- Authors
Surya, Sowmya; Horowitz, Jeffrey F; Goldenberg, Naila; Sakharova, Alla; Harber, Matthew; Cornford, Andrea S; Symons, Kathy; Barkan, Ariel L
- Abstract
<bold>Context: </bold>It is unclear whether the pattern of GH delivery to peripheral tissues has important effects.<bold>Objective: </bold>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.<bold>Setting: </bold>The study was conducted at the General Clinical Research Center at the University of Michigan Medical Center.<bold>Participants: </bold>Four men and five women with abdominal obesity (body mass index, 33 +/- 3 kg/m(2); body fat, 40 +/- 3%) participated in the study.<bold>Intervention: </bold>GH (0.5 mg/m(2) . 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.<bold>Main Outcome Measures: </bold>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.<bold>Results: </bold>The increase in plasma IGF-I concentrations was greater (P < 0.05) with continuous GH infusion (211 +/- 31, 423 +/- 38, and 309 +/- 34 microg/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 mumol/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.<bold>Conclusion: </bold>These findings indicate that, in obese subjects, discrete components of GH secretory pattern may differentially affect IGF-I generation and lipolytic responses.
- Subjects
GLUCOSE metabolism; COMPARATIVE studies; GENETIC disorders; HUMAN reproduction; LIPID metabolism disorders; RESEARCH methodology; MEDICAL cooperation; OBESITY; RESEARCH; RESEARCH funding; SOMATOMEDIN; EVALUATION research; HUMAN growth hormone; SKELETAL muscle
- Publication
Journal of Clinical Endocrinology & Metabolism, 2009, Vol 94, Issue 8, p2828
- ISSN
0021-972X
- Publication type
journal article
- DOI
10.1210/jc.2009-0638