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

Division of Metabolism, Endocrinology, and Diabetes (S.S., N.G., A.S., K.S., A.L.B.) and Division of Kinesiology (J.F.H., M.H., A.S.C.), University of Michigan, Ann Arbor, Michigan 48109

Address all correspondence and requests for reprints to: Ariel Barkan, M.D., University of Michigan, Division of Metabolism, Endocrinology and Diabetes, 3920 Taubman Center, SPC 5354, Ann Arbor, Michigan 48109-5354. E-mail: abarkan{at}umich.edu.

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.