Cohen J L, Vinik A, Faller J, Fox I H
J Clin Invest. 1985 Jan;75(1):251-7. doi: 10.1172/JCI111681.
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.
开展了多项研究，以确定低血糖或低血糖时的胰高血糖素反应是否会增加I型糖原贮积病（葡萄糖-6-磷酸酶缺乏症）患者的尿酸生成。三名患有这种疾病的成年人患有高尿酸血症（血清尿酸，11.3 - 12.4mg/dl），尿酸肾清除率降低（肾尿酸清除率，1.1 - 3.1ml/min）。其中一名患者通过静脉输注葡萄糖1个月后，这些异常情况得到改善，提示低血糖及其对尿酸代谢和排泄的相关影响发挥了作用。药理剂量的胰高血糖素使血清尿酸从11.4mg/dl升至13.0mg/dl，氧嘌呤尿排泄增加9倍，放射性标记腺嘌呤核苷酸衍生的尿放射性增加65%，尿酸尿排泄增加90%。这些变化表明静脉注射胰高血糖素会增加ATP分解为其降解产物，从而刺激尿酸生成。为了观察血清胰高血糖素的生理变化是否调节ATP降解，在输注生理盐水和生长抑素期间比较了尿酸生成情况。在输注生理盐水期间，随着患者出现低血糖，血清尿酸、尿氧嘌呤、放射性和尿酸排泄均增加。尽管出现低血糖，但输注生长抑素抑制了这些增加，并使血浆胰高血糖素水平从平均81.3pg/ml降至52.2pg/ml。这些数据表明，低血糖可刺激葡萄糖-6-磷酸酶缺乏症患者的尿酸合成。胰高血糖素通过激活ATP降解为尿酸而促成这一反应。
