title: Thiazide diuretics exacerbate fructose-induced metabolic syndrome.
abstract: 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.
authors.affiliation: Division of Nephrology, Hypertension and Transplantation, University of Florida, Gainesville, Florida, USA.
authors.forename: Sirirat
authors.initials: S
authors.lastname: Reungjui
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Roncal
authors.forename: Wei
authors.initials: W
authors.lastname: Mu
authors.forename: Titte R
authors.initials: TR
authors.lastname: Srinivas
authors.forename: Dhavee
authors.initials: D
authors.lastname: Sirivongs
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Johnson
authors.forename: Takahiko
authors.initials: T
authors.lastname: Nakagawa
mesh_terms: D000493:Allopurinol / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004232:Diuretics / Q000009:adverse effects*; D005632:Fructose / Q000009:adverse effects; D006074:Gout Suppressants / Q000494:pharmacology / Q000627:therapeutic use; D006852:Hydrochlorothiazide / Q000009:adverse effects*; D006943:Hyperglycemia / Q000188:drug therapy; D006973:Hypertension / Q000188:drug therapy; D015228:Hypertriglyceridemia / Q000188:drug therapy; D033461:Hyperuricemia / Q000139:chemically induced*; D007008:Hypokalemia / Q000139:chemically induced*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D007668:Kidney / Q000378:metabolism; D008297:Male; D024821:Metabolic Syndrome / Q000139:chemically induced*; D009569:Nitric Oxide / Q000652:urine; D011188:Potassium / Q000494:pharmacology / Q000652:urine; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000652:urine; D014527:Uric Acid / Q000097:blood / Q000652:urine
chemical_list: D004232:Diuretics; D006074:Gout Suppressants; D007328:Insulin; D006852:Hydrochlorothiazide; D014527:Uric Acid; D005632:Fructose; D009569:Nitric Oxide; D000493:Allopurinol; D012964:Sodium; D011188:Potassium