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Inhibition of the Rise in FFA by Acipimox Partially Prevents GH-Induced Insulin Resistance in GH-Deficient Adults

Department of Endocrinology, University Hospital MAS, S-205 02 Malmo, Sweden

Address all correspondence and requests for reprints to: Dr. Mikael Segerlantz, Department of Endocrinology, University Hospital MAS, S-205 02 Malmo, Sweden. E-mail: mikael.segerlantz{at}skane.se

Abstract

To test the hypothesis that GH-induced insulin resistance is mediated by an increase in FFA levels we assessed insulin sensitivity after inhibiting the increase in FFA by a nicotine acid derivative, Acipimox, in nine GH-deficient adults receiving GH replacement therapy. The patients received in a double blind fashion either Acipimox (500 mg) or placebo before a 2-h euglycemic (plasma glucose, 5.5 ± 0.2 mmol/liter) hyperinsulinemic (serum insulin, 28.7 ± 6.3 mU/liter) clamp in combination with indirect calorimetry and infusion of [3-³H]glucose.

Acipimox decreased fasting FFA by 88% (P = 0.012) and basal lipid oxidation by 39% (P = 0.015) compared with placebo. In addition, the insulin-stimulated lipid oxidation was 31% (P = 0.0077) lower during Acipimox than during placebo. Acipimox increased insulin-stimulated total glucose uptake by 36% (P = 0.021) compared with placebo, which mainly was due to a 47% (P = 0.015) increase in glucose oxidation.

GH induced insulin resistance is partially prevented by inhibition of lipolysis by Acipimox.

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