Inhibition of lipolysis stimulates whole body glucose production and disposal in normal postabsorptive subjects

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-H-3]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) hom 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.