To define
glucose flux in a state of chronic endogenous
insulin excess, a patient with an
insulinoma was studied. Plasma
glucose,
insulin (IRI),
glucagon (IRG) and
glucose turnover ([3-3H]
glucose infusion) were measured before and after
insulinoma resection in the postabsorptive state (PA), during a
glucose infusion adjusted to attain euglycemia (before
insulinoma resection only) and following an intravenous
glucagon bolus (1 mg). Before
insulinoma resection, plasma
glucose was 55 mg/dl,
glucose production (Ra) and disappearance (Rd) were equal (1.6 mg/kg/min) and
glucose clearance was elevated (2.8 ml/kg/min) in PA. When glycemia was raised with a
glucose infusion to 77 mg/dl, Rd did not change; in contrast Ra dropped to zero. Plasma IRI and IRG concentrations were 0.7 ng/ml and 110 pg/ml respectively before
glucose infusion and remained constant throughout. After resection of the
insulinoma, glycemia in PA was 103 mg/dl, Ra and Rd were increased slightly to 1.9 mg/kg/min while the metabolic clearance of
glucose was decreased by 25% (2.1 ml/kg/min).
Glucagon stimulation pre- and postinsulinoma resection resulted in significant increases in glycemia and IRI. We conclude that
hypoglycemia with
insulinoma is a consequence of decreased
glucose production and increased
glucose clearance. Hepatic sensitivity to small increments in glycemia is markedly enhanced so as to fully suppress endogenous
glucose production at euglycemic levels in the absence of any change in IRI and IRG. The mechanisms controlling hepatic Ra in
insulinoma appear different from normal.