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 oxidatio n in the regulation of whole body glucose production and uptake in the basal state is still a matter of debate. This question was analyzed i n nine normal overnight fasted volunteers in whom glucose kinetics ([3 -H-3]glucose infusion) and substrate oxidation rates (indirect calorim etry) were measured during 10.5 h both under placebo conditions and du ring experimental antilipolysis induced by Acipimox given orally durin g the last 8 h of the study. During the last 2 h of the tests, the fol lowing 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 oxidat ion (+18 +/- 8 vs. -24 +/- 11 mg/min; P < 0.02). Protein catabolism ca lculated 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 abou t 75% of the increased glucose production. Thus, contrary to current o pinion, FFA suppression stimulates glucose production and whole body g lucose disposal in normal overnight fasted subjects.