title: Aldosterone aggravates glucose intolerance induced by high fructose.
abstract: We previously reported that aldosterone impaired vascular insulin signaling in vivo and in vitro. Fructose-enriched diet induces metabolic syndrome including hypertension, insulin resistance, hyperlipidemia and diabetes in animal. In the current study, we hypothesized that aldosterone aggravated fructose feeding-induced glucose intolerance in vivo. Rats were divided into five groups for six-week treatment; uninephrectomy (Unx, n=8), Unx+aldosterone (aldo, 0.75 µg/h, s.c., n=8), Unx+fructose (fruc, 10% in drinking water, n=8), Unx+aldo+fruc, (aldo+fruc, n=8), and Unx+aldo+fruc+spironolactone, a mineralocorticoid receptor antagonist (aldo+fruc+spiro, 20mg/kg/day, p.o., n=8). Aldo+fruc rats manifested the hypertension, and induced glucose intolerance compared to fruc intake rats assessed by oral glucose tolerance test, homeostasis model assessment of insulin resistance and hyperinsulinemic-euglycemic clamp study. Spironolactone, significantly improved the aldosterone-accelerated glucose intolerance. Along with improvement in insulin resistance, spironolactone suppressed upregulated mineralocorticoid receptor (MR) target gene, serum and glucocorticoid-regulated kinases-1 mRNA expression in skeletal muscle in aldo+fruc rats. In conclusion, these data suggested that aldosterone aggravates fructose feeding-induced glucose intolerance through MR activation.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan.
authors.forename: Shamshad J
authors.initials: SJ
authors.lastname: Sherajee
authors.forename: Kazi
authors.initials: K
authors.lastname: Rafiq
authors.forename: Daisuke
authors.initials: D
authors.lastname: Nakano
authors.forename: Hirohito
authors.initials: H
authors.lastname: Mori
authors.forename: Hideki
authors.initials: H
authors.lastname: Kobara
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Hitomi
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Fujisawa
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kobori
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Masaki
authors.forename: Akira
authors.initials: A
authors.lastname: Nishiyama
mesh_terms: D000450:Aldosterone / Q000494:pharmacology*; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D005632:Fructose; D018149:Glucose Intolerance / Q000097:blood*; D005951:Glucose Tolerance Test; D017874:Immediate-Early Proteins / Q000235:genetics*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology*; D018482:Muscle, Skeletal / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013148:Spironolactone / Q000494:pharmacology*; D000099184:Serum-Glucocorticoid Regulated Kinases
chemical_list: D000450:Aldosterone; D001786:Blood Glucose; D005632:Fructose; D017874:Immediate-Early Proteins; D007328:Insulin; D000451:Mineralocorticoid Receptor Antagonists; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger; D013148:Spironolactone; D000099184:Serum-Glucocorticoid Regulated Kinases
keywords: Aldosterone; Fructose; Insulin resistance