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: Shamshad J Sherajee, Kazi Rafiq, Daisuke Nakano, Hirohito Mori, Hideki Kobara, Hirofumi Hitomi, Yoshihide Fujisawa, Hiroyuki Kobori, Tsutomu Masaki, Akira Nishiyama
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 720 Issue 1-3 Pg. 63-8 (Nov 15 2013) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 24201309 (Publication Type: Journal Article)
• Copyright: © 2013 Published by Elsevier B.V.

Chemical References

• Blood Glucose
• Immediate-Early Proteins
• Insulin
• Mineralocorticoid Receptor Antagonists
• RNA, Messenger
• Spironolactone
• Fructose
• Aldosterone
• Protein Serine-Threonine Kinases
• serum-glucocorticoid regulated kinase

Topics

• Aldosterone (pharmacology)
• Animals
• Blood Glucose (analysis)
• Fructose
• Glucose Intolerance (blood)
• Glucose Tolerance Test
• Immediate-Early Proteins (genetics)
• Insulin (blood)
• Insulin Resistance
• Male
• Mineralocorticoid Receptor Antagonists (pharmacology)
• Muscle, Skeletal (metabolism)
• Protein Serine-Threonine Kinases (genetics)
• RNA, Messenger (metabolism)
• Rats
• Rats, Sprague-Dawley
• Spironolactone (pharmacology)