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1 Division of Endocrinology/Diabetes/Metabolism and the General Clinical Research Center, Temple University Health Sciences Center, Philadelphia, Pennsylvania 19140; and 2 Department of Surgery, University of Medicine and Dentistry of New Jersey, School of Osteopathic Medicine, Stratford, New Jersey 08084
Free fatty acids (FFA) have
been shown to inhibit insulin suppression of endogenous glucose
production (EGP). To determine whether this is the result of
stimulation by FFA of gluconeogenesis (GNG) or glycogenolysis (GL) or a
combination of both, we have determined rates of GNG and GL (with
2H2O) and EGP in 16 healthy nondiabetic
volunteers (11 males, 5 females) during euglycemic-hyperinsulinemic
(~450 pM) clamping performed either with or without simultaneous
intravenous infusion of lipid plus heparin. During insulin infusion,
FFA decreased from 571 to 30 µmol/l (P < 0.001), EGP
from 15.7 to 2.0 µmol · kg
1 · min1
(P < 0.01), GNG from 8.2 to 3.7 µmol · kg1 · min1
(P < 0.05), and GL from 7.4 to 
1.7
µmol · kg1 · min1
(P < 0.02). During insulin plus lipid/heparin
infusion, FFA increased from 499 to 1,247 µmol/l (P < 0.001). EGP decreased 64% less than during insulin alone
(5.1 ± 0.7 vs. 13.7 ± 3.4 µmol · kg1 · min1).
The decrease in GNG was not significantly different from the decrease
of GNG during insulin alone (2.6 vs. 4.5
µmol · kg1 · min1, not
significant). In contrast, GL decreased 66% less than during insulin
alone (3.1 vs. 9.2
µmol · kg1 · min1,
P < 0.05). We conclude that insulin suppressed EGP by
inhibiting GL more than GNG and that elevated plasma FFA levels
attenuated the suppression of EGP by interfering with insulin
suppression of GL.
gluconeogenesis; endogenous glucose production; glucagon; euglycemic-hyperinsulinemic clamping; free fatty acid
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