Aldosterone Stimulates Gene Expression of Hepatic Gluconeogenic Enzymes through the Glucocorticoid Receptor in a Manner Independent of the Protein Kinase B Cascade

Endocrine Journal

Ryo YAMASHITA²  Yasumichi MORI²  Yasushi KABURAGI¹  Taisuke KIKUCHI²  Hisahiko SEKIHARA²  Kazuki YASUDA¹  Kazutaka AOKI² 

[1] Department of Metabolic Disorder, Research Institute, International Medical Center of Japan;Department of Endocrinology and Metabolism, Yokohama City University Graduate School of Medicine

关键词: Aldosterone;    Gluconeogenesis;    Glucocorticoid;    Mineralocorticoid;    Primary aldosteronism;   

DOI  :  10.1507/endocrj.51.243

学科分类：内分泌与代谢学

来源: Japan Endocrine Society

【 摘 要 】

References(35)Cited-By(13)Primary aldosteronism is associated with glucose intolerance and diabetes, which is due in part to impaired insulin release caused by reduction of potassium, although other possibilities remain to be elucidated. To evaluate the in vivo effects of aldosterone on glucose metabolism, a single dose of aldosterone was administered to mice, which resulted in elevation of the blood glucose level. In primary cultured mouse hepatocytes, the gene expression of gluconeogenic enzymes such as glucose-6-phosphatase (G6Pase), fructose-1,6-bisphosphatase and phosphoenolpyruvate carboxykinase increased in response to aldosterone in a dose-dependent manner even at a concentration similar to a physiological condition (10–9 M). The inhibitory effect of insulin on G6Pase gene expression was partially suppressed by aldosterone. Furthermore, aldosterone enhanced G6Pase promoter activity in human hepatoma cell line HepG2, which was prevented by co-treatment with a glucocorticoid antagonist RU-486, but not a mineralocorticoid antagonist spironolactone. In contrast, aldosterone had no effects on major insulin signaling pathways including insulin receptor substrate-1, protein kinase B, and forkhead transcription factor. These results suggest that aldosterone may affect the inhibitory effect of insulin on hepatic gluconeogenesis through the glucocorticoid receptor, which may be one of the causes of impaired glucose metabolism in primary aldosteronism.

【 授权许可】

Unknown