Acipimox increases glucose disposal in normal man independent of changes in plasma nonesterified fatty acid concentration and whole-body lipid oxidation rate

Metabolism. 1993 Mar;42(3):308-14. doi: 10.1016/0026-0495(93)90079-4.

Abstract

The short-term administration of a nicotinic acid analogue (acipimox) increases insulin sensitivity and consequently glucose disposal, both in patients with non-insulin-dependent diabetes mellitus (NIDDM) and in patients with cirrhosis. This effect has been attributed to a decrease in plasma nonesterified fatty acid (NEFA) levels and fatty acid oxidation rates, and a corresponding increase in carbohydrate oxidation. The aim of the present study was to determine whether acipimox influenced glucose disposal independent of changes in lipid metabolism. Seven normal men (age, 31 +/- 4 years; body mass index, 23.2 +/- 1.8 kg.m-2; fat-free mass [FFM], 66.8 +/- 4.2 kg) were studied on two separate occasions with hyperinsulinemic (0.06 U.kg FFM-1.h-1) euglycemic clamps (duration, 150 minutes). A primed (150 U), continuous (0.4 U.kg-1.min-1) infusion of heparin together with 10% intralipid (25 mL.h-1) was infused in both studies from -90 to 150 minutes to maintain comparable levels of plasma NEFA and lipid oxidation rates. Acipimox (500-mg capsules) or placebo were administered orally in a double-blind random fashion at t = -90 and t = 0 minutes. Whole-body lipid and carbohydrate oxidation were measured in the last 30 minutes of both the basal (preclamp) period (-30 to 0 minutes) and the clamp period (120 to 150 minutes).(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alanine / blood
  • C-Peptide / blood
  • Diabetes Mellitus, Type 2 / blood
  • Double-Blind Method
  • Fatty Acids, Nonesterified / blood*
  • Glucagon / blood
  • Glucose / metabolism*
  • Glycerol / blood
  • Growth Hormone / blood
  • Humans
  • Hydroxybutyrates / blood
  • Hypolipidemic Agents / administration & dosage
  • Hypolipidemic Agents / pharmacology*
  • Insulin / blood
  • Lactates / blood
  • Lipid Metabolism*
  • Male
  • Oxidation-Reduction
  • Pyrazines / administration & dosage
  • Pyrazines / pharmacology*
  • Pyruvates / blood
  • Radioimmunoassay
  • Time Factors

Substances

  • C-Peptide
  • Fatty Acids, Nonesterified
  • Hydroxybutyrates
  • Hypolipidemic Agents
  • Insulin
  • Lactates
  • Pyrazines
  • Pyruvates
  • Growth Hormone
  • Glucagon
  • Glucose
  • acipimox
  • Alanine
  • Glycerol