Reungjui Sirirat, Roncal Carlos A, Mu Wei, Srinivas Titte R, Sirivongs Dhavee, Johnson Richard J, Nakagawa Takahiko
Division of Nephrology, Hypertension and Transplantation, University of Florida, Gainesville, Florida, USA.
J Am Soc Nephrol. 2007 Oct;18(10):2724-31. doi: 10.1681/ASN.2007040416. Epub 2007 Sep 12.
Fructose is a commonly used sweetener associated with diets that increase the prevalence of metabolic syndrome. Thiazide diuretics are frequently used in these patients for treatment of hypertension, but they also exacerbate metabolic syndrome. Rats on high-fructose diets that are given thiazides exhibit potassium depletion and hyperuricemia. Potassium supplementation improves their insulin resistance and hypertension, whereas allopurinol reduces serum levels of uric acid and ameliorates hypertension, hypertriglyceridemia, hyperglycemia, and insulin resistance. Both potassium supplementation and treatment with allopurinol also increase urinary nitric oxide excretion. We suggest that potassium depletion and hyperuricemia in rats exacerbates endothelial dysfunction and lowers the bioavailability of nitric oxide, which blocks insulin activity and causes insulin resistance during thiazide usage. Addition of potassium supplements and allopurinol with thiazides might be helpful in the management of metabolic syndrome.
果糖是一种常用甜味剂,与增加代谢综合征患病率的饮食有关。噻嗪类利尿剂常用于这些患者治疗高血压,但它们也会加重代谢综合征。给予噻嗪类药物的高果糖饮食大鼠会出现钾缺乏和高尿酸血症。补充钾可改善其胰岛素抵抗和高血压,而别嘌醇可降低血清尿酸水平,并改善高血压、高甘油三酯血症、高血糖和胰岛素抵抗。补充钾和用别嘌醇治疗还会增加尿一氧化氮排泄。我们认为,大鼠体内的钾缺乏和高尿酸血症会加剧内皮功能障碍,并降低一氧化氮的生物利用度,这在使用噻嗪类药物期间会阻断胰岛素活性并导致胰岛素抵抗。在噻嗪类药物中添加钾补充剂和别嘌醇可能有助于管理代谢综合征。