We have quantitatively determined gluconeogenesis (GNG) from all precursors
, using a novel method employing (H2O)-H-2 to address the question of wheth
er changes in plasma free fatty acids (FFA) affect GNG in healthy, nonobese
subjects. In the first study (n = 6), plasma FFA were lowered at 16 to 20
hours with nicotinic acid (NA) and were then allowed to rise at 20 to 24 ho
urs (FFA rebound after administration of NA). FFA decreased from 387 mu M a
t 16 hours to 43 mu M at 20 hours, and then rebounded to 1,823 mu M at 24 h
ours. GNG decreased from 58.1% at 16 hours to 38.6% of endogenous glucose p
roduction at 20 hours (P < 0.005) and then rebounded to 78.9% at 24 hours (
P < 0.05). Conversely, glycogenolysis (GL) increased from 41.9% at 16 hours
to 61.4% at 20 hours (P < 0.05), and then decreased to 21.1% at 24 hours (
P < 0.05). In the second study (controls; n = 6), volunteers were analyzed
between 16 and 24 hours after the last meal. FFA rose from 423 to 681 mu M
(P < 0.05), and GNG from 50.3% to 61.7% (P < 0.02), whereas GL decreased fr
om 49.7% to 38.3% (P < 0.05). Endogenous glucose production decreased at th
e same rate in both studies, from 10.7 to 8.6 mu mol/kg/min (P < 0.05). In
study 3 (n = 6), in which the NA-mediated decrease of plasma FFA was preven
ted by infusion of lipid and heparin, neither FFA nor GNG changed significa
ntly. In summary, our data suggest that (a) acute changes in plasma FFA pro
duce acute changes in GNG and reciprocal changes in GL; (b) the decrease in
EGP between 16 and 24 hours of fasting is due to a fall in GL; and (c) NA
has no direct effect on GNG.