title: Down-regulation of hepatic phosphoenolpyruvate carboxykinase expression in magnesium-deficient rats.
abstract: Many epidemiological studies have reported the link between magnesium deficiency and metabolic syndrome. We examined whether magnesium deficiency in rats induces changes in glucocorticoid metabolism. Twelve-week-old, female Wistar rats were weaned onto a very low-magnesium diet or a control diet for two weeks. Quantitative real-time PCR was used to assess mRNA for 11β hydroxysteroid dehydrogenase-1 (11β-HSD1), 11β-HSD2, phosphoenolpyruvate carboxykinase (PEPCK), peroxisome proliferator-activated receptor α (PPARα), and glucocorticoid receptor in the liver. Concentrations of adiponectin, leptin, corticosterone, insulin and asymmetric dimethylarginine (ADMA) in fasting serum were determined using a rat-specific enzyme-linked immunosorbent assay. After two weeks, no differences in serum glucose, leptin, corticosterone, or adiponectin levels were observed between the groups. Magnesium-deficient rats showed higher HOMA-IR, insulin, ionized calcium, ADMA levels and diastolic blood pressure. There were no significant differences in hepatic mRNA expression levels of GR, 11β-HSD1, 11β-HSD2, or PPARα between the groups. We observed lower expression of hepatic PEPCK mRNA, in the magnesium-deficient rats, thus suggesting a possible compensatory mechanism to diminish glycogenesis. A low-magnesium diet alters glucocorticoid metabolism, which leads to endothelial damage. Higher ADMA induces hypertension and insulin resistance. Hyperinsulinemia induces hepatic down-regulation of PEPCK, and is possibly a key mechanism inducing the metabolic complications of magnesium deficiency.
authors.affiliation: Department of Pediatrics, Kansai Medical University, Fumizono-cho, Moriguchi-shi, Osaka, Japan. takaya@takii.kmu.ac.jp
authors.forename: Junji
authors.initials: J
authors.lastname: Takaya
authors.forename: Anna
authors.initials: A
authors.lastname: Iharada
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Okihana
authors.forename: Kazunari
authors.initials: K
authors.lastname: Kaneko
mesh_terms: D000818:Animals; D015536:Down-Regulation / Q000235:genetics*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics*; D008099:Liver / Q000201:enzymology* / Q000378:metabolism; D008275:Magnesium Deficiency / Q000235:genetics* / Q000378:metabolism; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D012333:RNA, Messenger; D010729:Phosphoenolpyruvate Carboxykinase (GTP)