Increased endogenous
glucose production (EGP) and gluconeogenesis contribute to the pathogenesis of hyperglycaemia in
non-insulin-dependent diabetes mellitus (
NIDDM). In healthy subjects, however, EGP remains constant during administration of gluconeogenic precursors. This study was performed in order to determine whether administration of
fructose increases EGP in obese
NIDDM patients and obese non-diabetic subjects. Eight young healthy lean subjects, eight middle-aged obese
NIDDM patients and seven middle-aged obese non-diabetic subjects were studied during hourly ingestion of 13C
fructose (0.3 g.kg fat free mass-1.h-1) for 3 h.
Fructose failed to increase EGP (measured with 6,6 2H
glucose) in
NIDDM (17.7 +/- 1.9 mumol.kg fat free mass-1.min-1 basal vs 15.9 +/- 0.9 after
fructose), in obese non-diabetic subjects (12.1 +/- 0.5 basal vs 13.1 +/- 0.5 after
fructose) and in lean healthy subjects (13.3 +/- 0.5 basal vs 13.8 +/- 0.6 after
fructose) although 13C
glucose synthesis contributed 73.2% of EGP in lean subjects, 62.6% in obese non-diabetic subjects, and 52.8% in obese
NIDDM patients. Since
glucagon may play an important role in the development of hyperglycaemia in
NIDDM, healthy subjects were also studied during 13C
fructose ingestion + hyperglucagonaemia (232 +/- 9 ng/l) and during hyperglucagonaemia alone. EGP increased by 19.8% with ingestion of
fructose +
glucagon (p < 0.05) but remained unchanged during administration of
fructose or
glucagon alone. The plasma 13C
glucose enrichment was identical after
fructose ingestion both with and without
glucagon, indicating that the contribution of
fructose gluconeogenesis to the
glucose 6-phosphate pool was identical in these two conditions. We concluded that during
fructose administration: 1) gluconeogenesis is increased, but EGP remains constant in
NIDDM, obese non-diabetic, and lean individuals; 2) in lean individuals, both an increased glucagonaemia and an enhanced supply of gluconeogenic precursors are required to increase EGP; this increase in EGP occurs without changes in the relative proportion of
glucose 6-phosphate production from
fructose and from other sources (i.e. glycogenolysis + gluconeogenesis from non-
fructose precursors).