Growth hormone-induced insulin resistance is associated with increased intramyocellular triglyceride content but unaltered VLDL-triglyceride kinetics

Morten B. Krag, Lars C. Gormsen, Zeng Kui Guo, Jens S. Christiansen, Michael D. Jensen, Søren Nielsen, Jens O.L. Jørgensen

Research output: Contribution to journalArticlepeer-review

65 Scopus citations

Abstract

The ability of growth hormone (GH) to stimulate lipolysis and cause insulin resistance in skeletal muscle may be causally linked, but the mechanisms remain obscure. We investigated the impact of GH on the turnover of FFA and VLDL-TG, intramuscular triglyceride content (IMTG), and insulin sensitivity (euglycemic clamp) in nine healthy men in a randomized double-blind placebo-controlled crossover study after 8 days treatment with (A) Placebo + Placebo, (B) GH (2 mg daily) + Placebo, and (C) GH (2 mg daily) + Acipimox (250 mg x 3 daily). In the basal state, GH (B) increased FFA levels (P < 0.05), palmitate turnover (P < 0.05), and lipid oxidation (P = 0.05), but VLDL-TG kinetics were unaffected. Administration of acipimox (C) suppressed basal lipolysis but did not influence VLDL-TG kinetics. In the basal state, IMTG content increased after GH (B; P = 0.03). Insulin resistance was induced by GH irrespective of concomitant acipimox (P < 0.001). The turnover of FFA and VLDL-TG was suppressed by hyperinsulinemia during placebo and GH, whereas coadministration of acipimox induced a rebound increase FFA turnover and VLDL-TG clearance. We conclude that these results show that GH-induced insulin resistance is associated with increased IMTG and unaltered VLDL-TG kinetics; we hypothesize that fat oxidation in muscle tissue is an important primary effect of GH and that circulating FFA rather than VLDL-TG constitute the major source for this process; and the role of IMTG in the development of GH-induced insulin resistance merits future research.

Original languageEnglish (US)
Pages (from-to)E920-E927
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume292
Issue number3
DOIs
StatePublished - Mar 2007

Keywords

  • Acipimox
  • Hyperinsulinemic euglycemic clamp
  • Insulin sensitivity
  • Lipolysis
  • Very-low-density lipoprotein-triglyceride kinetics

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

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