To determine the effect of inhibition of gluconeogenesis on
liver glycogen stores in patients with
non-insulin-dependent diabetes mellitus (
NIDDM) after a 3-day fast, 10%
ethanol (EtOH) was administered intravenously to nine obese patients with
NIDDM and six obese nondiabetic subjects. Rates of
glucose appearance (3-[3H]
glucose) and [U-14C]
alanine incorporation into
glucose (
alanine gluconeogenesis [Ala-GNG]) were determined before and during EtOH administration, and residual
glycogen stores were assessed by the incremental
glucose response to
glucagon (glucoseAUC). Hepatic
glucose output (HGO) was closely correlated with plasma
glucose levels (r = 0.71, P < 0.001) after the 3-day fast and was significantly greater in the diabetic compared with the nondiabetic subjects (13.8 +/- 1.4 vs. 7.6 +/- 0.6 mumol.kg-1 FFM.min-1, P < 0.01). During the 120-min EtOH infusion, Ala-GNG fell by more than 50% in both groups and did not increase after intravenous
glucagon administration. HGO fell modestly in both the diabetic and nondiabetic subjects during the first 30 min of EtOH infusion and stabilized thereafter. In contrast to Ala-GNG, HGO increased significantly after intravenous
glucagon administration in both the diabetic and nondiabetic subjects, but the increase was significantly greater in the patients with
NIDDM (P < 0.01). The
glucose area under the curve in response to
glucagon (glucoseAUC) was lower in the presence of EtOH than in its absence (14.9 +/- 7 vs. 68 +/- 15.6 mM/min, P < 0.01) in the obese nondiabetic subjects, which suggests a decrease in
liver glycogen stores.(ABSTRACT TRUNCATED AT 250 WORDS)