Inhibition of lipolysis decreases lipid oxidation and gluconeogenesis from lactate but not fasting hyperglycemia or total hepatic glucose production in NIDDM.
We determined whether overnight inhibition of lipolysis by a long-acting nicotinic acid derivative (acipimox) decreases gluconeogenesis from lactate in NIDDM patients. For this purpose, 250 mg of acipimox or placebo was administered in a double-blind crossover study at 2400, 0400, and 0800 to 8 NIDDM patients (54 +/- 4 yr of age, body mass index 29.5 +/- 1.3 kg/m2, fasting plasma glucose 11 +/- 1 mM). The next morning, total hepatic glucose production (glucose Ra) and gluconeogenesis from lactate were determined using primed, continuous infusions of [3-3H]glucose and [U-14C]acetate. Glucose and lipid oxidation rates were measured using indirect calorimetry. Mean overnight serum free fatty acid concentrations averaged 242 +/- 8 microM after acipimox and 721 +/- 30 microM after placebo (P < 0.001). Inhibition of lipolysis decreased lipid oxidation from 33 +/- 3 to 22 +/- 2 J.kg-1 x min-1 (P < 0.001) and increased carbohydrate oxidation from 15 +/- 3 to 23 +/- 2 mumol.kg-1.min-1 (P < 0.005). Gluconeogenesis from lactate decreased by approximately 40%, from 6.2 +/- 0.6 to 3.8 +/- 0.5 mumol.kg-1 x min-1 (P < 0.005); lactate oxidation increased from 5.6 +/- 0.8 to 7.9 +/- 1.1 mumol.kg-1 x min-1 (P < 0.005), with no change in plasma lactate concentrations or total lactate Rd. Fasting plasma glucose concentrations were comparable at 2400 (10.0 +/- 1.1 vs. 10.6 +/- 1.3 mM, acipimox vs. placebo) and between 0900 and 1000 (10.6 +/- 1.3 and 11.3 +/- 1.3 mM, respectively). Also, total glucose production rates remained unchanged (14.0 +/- 1.2 vs. 14.9 +/- 1.3 mol.kg-1 x min-1, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
Puhakainen
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Second Department of Medicine, University of Helsinki, Finland.
Yki-Järvinen
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D000704:Analysis of Variance; D001786:Blood Glucose / Q000378:metabolism*; D002250:Carbon Radioisotopes; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D004311:Double-Blind Method; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005934:Glucagon / Q000097:blood; D005943:Gluconeogenesis / Q000187:drug effects*; D013006:Growth Hormone / Q000097:blood; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D007773:Lactates / Q000097:blood / Q000378:metabolism*; D008066:Lipolysis / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010101:Oxygen Consumption / Q000187:drug effects; D011719:Pyrazines / Q000494:pharmacology*; D014316:Tritium
D001786:Blood Glucose; D002250:Carbon Radioisotopes; D005230:Fatty Acids, Nonesterified; D000960:Hypolipidemic Agents; D007773:Lactates; D011719:Pyrazines; D014316:Tritium; D013006:Growth Hormone; D005934:Glucagon; C027696:acipimox; D006854:Hydrocortisone