Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.1.1.32 (phosphoenolpyruvate carboxykinase)
 4,204 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mineralocorticoid receptor (MR) is expressed in kidney and plays a central role in the control of sodium, homeostatic fluid, and blood pressure. It has also been implicated in other functions in cardiovascular system, central nervous system, and adipose tissue. This study revealed a novel role of MR in the gene regulation related to hepatic glucose production. RNAi-mediated MR silencing led to a decrease in the expression of glucose-6-phosphatase (G6Pase), phosphoenolpyruvate carboxykinase, and fructose-1,6-bisphosphatase 1, the enzymes known to be involved in glucose production in liver. The MR-specific antagonists also down-regulated the expression of G6Pase, while the specific agonist enhanced G6Pase expression. These observations, for the first time, revealed a novel role for MR and its ligands in the regulation of de novo glucose synthesis in hepatocytes. It also suggests the potential of liver-specific MR modulation for the treatment of hyperglycemia.
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PMID:Mineralocorticoid receptor is involved in the regulation of genes responsible for hepatic glucose production. 1651 49

Low birth weight (LBW) is associated with type 2 diabetes and depression, which may be related to prenatal stress and insulin resistance as a result of chronic hypothalamic-pituitary-adrenal (HPA) axis hyperactivity. We examined whether treatment with a selective serotonin reuptake inhibitor [escitalopram (ESC)] could downregulate HPA axis activity and restore insulin sensitivity in LBW rats. After 4-5 wk of treatment, ESC-exposed LBW (SSRI-LBW) and saline-treated control and LBW rats (Cx and LBW) underwent an oral glucose tolerance test or a hyperinsulinemic euglycemic clamp to assess whole body insulin sensitivity. Hepatic phosphoenolpyruvate carboxykinase (PEPCK) mRNA expression and red skeletal muscle PKB Ser(473) phosphorylation were used to assess tissue-specific insulin sensitivity. mRNA expression of the hypothalamic mineralocorticoid receptor was fivefold upregulated in LBW (P < 0.05 vs. Cx), accompanied by increased corticosterone release during restraint stress and total 24-h urinary excretion (P < 0.05 vs. Cx), whole body insulin resistance (P < 0.001 vs. Cx), and impaired insulin suppression of hepatic PEPCK mRNA expression (P < 0.05 vs. Cx). Additionally, there was a tendency for reduced red muscle PKB Ser(473) phosphorylation. The ESC treatment normalized corticosterone secretion (P < 0.05 vs. LBW), whole body insulin sensitivity (P < 0.01) as well as postprandial suppression of hepatic mRNA PEPCK expression (P < 0.05), and red muscle PKB Ser(473) phosphorylation (P < 0.01 vs. LBW). We conclude that these data suggest that the insulin resistance and chronic HPA axis hyperactivity in LBW rats can be reversed by treatment with an ESC, which downregulates HPA axis activity, lowers glucocorticoid exposure, and restores insulin sensitivity in LBW rats.
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PMID:Treatment with an SSRI antidepressant restores hippocampo-hypothalamic corticosteroid feedback and reverses insulin resistance in low-birth-weight rats. 2010 38

Recent evidence suggests that treatment with mineralocorticoid receptor antagonist suppressed local inflammation in vascular tissues or cardiomyocytes; therefore, we examined the effect of spironolactone on glucose and lipid metabolism in a mouse model with diet-induced diabetes and nonalcoholic fatty liver disease. C57BL/6 mice were fed either the control diet, 60% fat diet with 30% fructose water (HFFD), or HFFD with spironolactone for 8 wk. HFFD mice demonstrated apparent phenotypes of metabolic syndrome, including insulin resistance, hypertension, dyslipidemia, and fatty liver. Although treatment with spironolactone did not affect the increased calorie intake and body weight by HFFD, the increments of epididymal fat weight, blood pressure, serum triglyceride, free fatty acids, leptin, and total cholesterol levels were significantly suppressed. Elevation of blood glucose during glucose and insulin tolerance tests in HFFD mice was significantly lowered by spironolactone. Notably, increased glucose levels during pyruvate tolerance test in HFFD mice were almost completely ameliorated to control levels by the treatment. Staining with hematoxylin-eosin (HE) and Oil-red-O demonstrated marked accumulation of triglycerides in the centrilobular part of the hepatic lobule in HFFD mice, and these accumulations were effectively improved by spironolactone. Concomitantly HFFD feeding markedly up-regulated hepatic mRNA expression of proinflammatory cytokines (TNFalpha, IL-6, and monocyte chemoattractant protein-1), gluconeogenic gene phosphoenolpyruvate carboxykinase, transcription factor carbohydrate response element binding protein, and its downstream lipogenic enzymes, all of which were significantly suppressed by spironolactone. These results indicate that inhibition of mineralocorticoid receptor might be a beneficial therapeutic approach for diet-induced phenotypes of metabolic syndrome and fatty liver.
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PMID:Spironolactone improves glucose and lipid metabolism by ameliorating hepatic steatosis and inflammation and suppressing enhanced gluconeogenesis induced by high-fat and high-fructose diet. 2021 73