Studies were performed to determine whether
hypoglycemia or the
glucagon response to
hypoglycemia increases
uric acid production in
glycogen storage disease type I (glucose-6-phosphatase deficiency). Three adults with this disease had
hyperuricemia (serum
urate, 11.3-12.4 mg/dl) and reduced renal clearance of
urate (renal
urate clearance, 1.1-3.1 ml/min). These abnormalities were improved in one patient by intravenous
glucose infusion for 1 mo, suggesting a role for
hypoglycemia and its attendant effects on
urate metabolism and excretion. A pharmacologic dose of
glucagon caused a rise in serum
urate from 11.4 to 13.0 mg/dl, a ninefold increase in urinary excretion of oxypurines, a 65% increase in urinary radioactivity derived from radioactively labeled
adenine nucleotides, and a 90% increase in urinary
uric acid excretion. These changes indicate that intravenous
glucagon increases
ATP breakdown to its degradation products and thereby stimulates
uric acid production. To observe whether physiologic changes in serum
glucagon modulate
ATP degradation,
uric acid production was compared during saline and
somatostatin infusions. Serum
urate, urinary oxypurine, radioactivity, and
uric acid excretion increased during saline infusion as patients became
hypoglycemic. Infusion of
somatostatin suppressed these increases despite
hypoglycemia and decreased the elevated plasma
glucagon levels from a mean of 81.3 to 52.2 pg/ml. These data suggest that
hypoglycemia can stimulate
uric acid synthesis in
glucose-6-phosphatase deficiency.
Glucagon contributes to this response by activating
ATP degradation to
uric acid.