The Pattern of Growth Hormone Delivery to Peripheral Tissues Determines Insulin-Like Growth Factor-1 and Lipolytic Responses in Obese Subjects

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.