Acipimox increases glucose disposal in normal man independent of changes in plasma nonesterified fatty acid concentration and whole-body lipid oxidation rate.
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)
Fulcher
G R
GR
Department of Medicine, University of Newcastle-upon-Tyne, England.
Walker
M
M
Farrer
M
M
Johnson
A S
AS
Alberti
K G
KG
D000328:Adult; D000409:Alanine / Q000097:blood; D002096:C-Peptide / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood; D004311:Double-Blind Method; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D005934:Glucagon / Q000097:blood; D005947:Glucose / Q000378:metabolism*; D005990:Glycerol / Q000097:blood; D013006:Growth Hormone / Q000097:blood; D006801:Humans; D006885:Hydroxybutyrates / Q000097:blood; D000960:Hypolipidemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D007773:Lactates / Q000097:blood; D050356:Lipid Metabolism; D008297:Male; D010084:Oxidation-Reduction; D011719:Pyrazines / Q000008:administration & dosage / Q000494:pharmacology*; D011773:Pyruvates / Q000097:blood; D011863:Radioimmunoassay; D013997:Time Factors
D002096:C-Peptide; D005230:Fatty Acids, Nonesterified; D006885:Hydroxybutyrates; D000960:Hypolipidemic Agents; D007328:Insulin; D007773:Lactates; D011719:Pyrazines; D011773:Pyruvates; D013006:Growth Hormone; D005934:Glucagon; D005947:Glucose; C027696:acipimox; D000409:Alanine; D005990:Glycerol