Blog
About

  • Record: found
  • Abstract: found
  • Article: not found

Direct regulation of glucose and not insulin on hepatic hexose-6-phosphate dehydrogenase and 11β-hydroxysteroid dehydrogenase type 1.

Molecular and Cellular Endocrinology

11-beta-Hydroxysteroid Dehydrogenase Type 1, genetics, metabolism, Animals, Blotting, Western, Carbohydrate Dehydrogenases, Cells, Cultured, Diabetes Mellitus, Experimental, Diabetes Mellitus, Type 2, Disease Models, Animal, Fasting, Gene Expression, Gluconeogenesis, Glucose, pharmacology, Glucose-6-Phosphate, Hepatocytes, enzymology, Hyperglycemia, Insulin, Liver, Polymerase Chain Reaction, Rats

Read this article at

ScienceOpenPublisherPMC
Bookmark
      There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

      Abstract

      Abnormal hepatic gluconeogenesis contributes significantly to both fasting and non-fasting hyperglycemia of patients with type 2 diabetes. 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) regulates the key hepatic gluconeogenic enzymes including phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) through the amplification of glucocorticoid receptor (GR) - mediated tissue glucocorticoid action, and is crucially dependent on hexose-6-phosphate dehydrogenase (H6PDH) - generating NADPH system. Here, we observed that compared with fasting state, H6PDH and 11β-HSD1 expression in livers were all increased under non-fasting state in both normal and diabetic rats, and the non-fasting diabetic group was the highest among the four experimental groups. Moreover, incubation of primary hepatocytes with increasing glucose caused dose-dependent increases in H6PDH, 11β-HSD1, GR, PEPCK and G6Pase expression. Also, glucose-6-phosphate (G6P) had a positive regulation on H6PDH and 11β-HSD1 in hepatocytes. In addition, primary hepatocytes treated with different doses of insulin in high glucose induced alteration of H6PDH and 11β-HSD1 while in low glucose there was no significant effect. These findings suggest that glucose instead of insulin directly regulates H6PDH and 11β-HSD1 and suppression of the two enzymes could be considered as an effective target for the treatment of type 2 diabetes. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

      Related collections

      Author and article information

      Journal
      10.1016/j.mce.2010.12.010
      3741409
      21163329

      Comments

      Comment on this article