title: Spironolactone prevents dietary-induced metabolic syndrome by inhibiting PI3-K/Akt and p38MAPK signaling pathways.
abstract: OBJECTIVE
  Aim of the study is to evaluate the impact of spironolactone (SPL) on indexes of metabolic syndrome (MS) and further investigate the mechanisms underlying its protective effects.
  
  
  METHODS
  A rat model of MS was established by administering a fat- and salt-enriched diet (FS diet). The occurrence of MS was examined by measurement of blood pressure (BP), aldosterone (ALD) content, blood lipid (BL), glucose and insulin levels. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Pancreatic gland tissue injury was assessed by β-cell apoptosis. Mineralocorticoid receptor (MR) activity, phosphatidylinositol 3- kinase/Akt (PI3-K/Akt), and phosphorylation of p38MAPK (Pp38MAPK) in pancreatic gland tissue were evaluated by western blot analysis.
  
  
  RESULTS
  SPL prevented hypertension, and dyslipidemia during MS induced by the intake of FS diet, but had no effect on K+ and Na+ disturbances. Furthermore, SPL significantly attenuated ALD and MR expression levels after FS diet. Finally, SPL inhibited phosphorylation protein kinase B (p- PKB) activation in the pancreatic gland tissue, a downstream target of PI3-K, and phosphorylation of p38MAPK pathway, critical for cellular apoptosis.
  
  
  CONCLUSIONS
  This study demonstrates that SPL exerts a protective effect on hypertension and dyslipidemia. This protective effect may depend, at least in part, on MAPK and PI3-K pathways.
authors.affiliation: Department of Internal Medicine, Affiliated Tumor Hospital of Guangzhou Medical College, Guangzhou, Guangdong Province, China.
authors.forename: H D
authors.initials: HD
authors.lastname: Long
authors.forename: Y E
authors.initials: YE
authors.lastname: Lin
authors.forename: M J
authors.initials: MJ
authors.lastname: Liu
authors.forename: L Y
authors.initials: LY
authors.lastname: Liang
authors.forename: Z H
authors.initials: ZH
authors.lastname: Zeng
mesh_terms: D000450:Aldosterone / Q000096:biosynthesis; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D059305:Diet, High-Fat / Q000009:adverse effects*; D050171:Dyslipidemias / Q000517:prevention & control; D006973:Hypertension / Q000517:prevention & control; D050417:Insulin-Secreting Cells / Q000187:drug effects; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D024821:Metabolic Syndrome / Q000517:prevention & control*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D018161:Receptors, Mineralocorticoid / Q000096:biosynthesis; D017673:Sodium Chloride, Dietary / Q000009:adverse effects*; D013148:Spironolactone / Q000627:therapeutic use*
chemical_list: D018161:Receptors, Mineralocorticoid; D017673:Sodium Chloride, Dietary; D013148:Spironolactone; D000450:Aldosterone; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt