title: Inhibition of lipolysis stimulates whole body glucose production and disposal in normal postabsorptive subjects.
abstract: The role played by circulating free fatty acids (FFA) and fat oxidation in the regulation of whole body glucose production and uptake in the basal state is still a matter of debate. This question was analyzed in nine normal overnight fasted volunteers in whom glucose kinetics ([3-3H]glucose infusion) and substrate oxidation rates (indirect calorimetry) were measured during 10.5 h both under placebo conditions and during experimental antilipolysis induced by Acipimox given orally during the last 8 h of the study. During the last 2 h of the tests, the following mean changes (delta) from baseline were recorded in Acipimox vs. placebo studies: delta FFA, -0.26 +/- 0.08 vs. +0.29 +/- 0.06 mmol/L (P < 0.001); delta glucose, -12 +/- 2 vs. -12 +/- 1 mg/dL (P > 0.05); delta glucose production, +16 +/- 5 vs. -15 +/- 3 mg/min (P < 0.001); delta C peptide, -1.11 +/- 0.10 vs. -0.66 +/- 0.10 ng/mL (P < 0.001); delta glucagon, +64 +/- 25 vs. +21 +/- 9 pg/mL (P < 0.05); delta GH, +37 +/- 9 vs. +4 +/- 2 ng/mL (P < 0.007); delta cortisol, +37 +/- 25 vs. -30 +/- 26 ng/mL (P < 0.04). Acipimox inhibited fat oxidation (-18 +/- 4 vs. +19 +/- 4 mg/min; P < 0.001) and enhanced carbohydrate oxidation (+18 +/- 8 vs. -24 +/- 11 mg/min; P < 0.02). Protein catabolism calculated over the 8-h study period was significantly stimulated (+5.7 +/- 2.5 vs. -1.9 +/- 1.7 g/8 h; P < 0.02). During the Acipimox studies, the increased protein breakdown could theoretically account for about 75% of the increased glucose production. Thus, contrary to current opinion, FFA suppression stimulates glucose production and whole body glucose disposal in normal overnight fasted subjects.
authors.affiliation: Laboratory of Experimental Medicine, Hôpital Erasme, University of Brussels, Belgium.
authors.forename: F
authors.initials: F
authors.lastname: Fery
authors.forename: L
authors.initials: L
authors.lastname: Plat
authors.forename: M
authors.initials: M
authors.lastname: Baleriaux
authors.forename: E O
authors.initials: EO
authors.lastname: Balasse
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D002153:Calorimetry, Indirect; D005215:Fasting; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006728:Hormones / Q000097:blood; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D008066:Lipolysis / Q000187:drug effects; D008297:Male; D009584:Nitrogen / Q000378:metabolism; D009994:Osmolar Concentration; D011719:Pyrazines / Q000494:pharmacology; D013997:Time Factors
chemical_list: D001786:Blood Glucose; D006728:Hormones; D000960:Hypolipidemic Agents; D011719:Pyrazines; D005947:Glucose; C027696:acipimox; D009584:Nitrogen