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/m(2); body fat, 40 +/- 3%) participated in the study.

Intervention: 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.

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 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.

Conclusion: These findings indicate that, in obese subjects, discrete components of GH secretory pattern may differentially affect IGF-I generation and lipolytic responses.

Figures

Figure 1

Mean 24-h GH profile for lean subjects under basal conditions (A), obese subjects under basal/control conditions (B), obese subjects pulsatile GH infusion (C), and obese subjects during continuous GH infusion (D). Relatively minor variability in timing of the GH pulses among the lean subjects distorts the GH profile to make the peak shapes more broad and less defined. se bars have been removed for clarity.

Figure 2

Plasma IGF-I concentration (A) and IGF-I mRNA abundance (B) in skeletal muscle during basal/control conditions, continuous GH infusion, and pulsatile GH infusion. *, Significantly different than basal conditions, P < 0.05. †, Significantly different from pulsatile, P < 0.05.

Figure 3

Glycerol rate of appearance in plasma (Ra), an index of whole-body lipolytic rate, during basal/control conditions, continuous GH infusion, and pulsatile GH infusion. *, Significantly different than basal conditions, P < 0.05.

Figure 4

Glucose Ra, an index of hepatic glucose production (A) and Matsuda Composite index, as a marker for insulin sensitivity (B) during basal/control conditions, continuous GH infusion, and pulsatile GH infusion. *, Significantly different than basal conditions, P < 0.05.