2
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      The 11β-hydroxysteroid dehydrogenase type 1 inhibitor protects against the insulin resistance and hepatic steatosis in db/db mice.

      Read this article at

      ScienceOpenPublisherPubMed
      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

          Glucocorticoids (GCs) metabolism is regulated by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). When GCs are present in excess, they can impair glucose-dependent insulin sensitivity. We have previously synthesized several curcumin analogues, of which four compounds were selective inhibitors of 11β-HSD1. Here, we present data supporting that the 11β-hydroxysteroid dehydrogenase type 1 inhibitor (H8) inhibits insulin resistance and ameliorates hepatic steatosis in db/db mice. We compared glucose and lipid metabolism in db/db mice with or without administration of H8, which significantly decreased fasting blood glucose levels and protected against insulin resistance and hepatic steatosis compared to when glucose and lipid metabolism were measured following curcumin administration. The hepatic enzyme was reduced significantly in the plasma samples from db/db mice which were treated with H8. Serum corticosterone (active) levels, which are regulated by 11β-HSD1 were reduced when mice received H8. H8 administration suppressed phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6-pase) expression, which are related to gluconeogenesis and enhanced glucose transporter 4 (GLUT4) protein content in liver. Treatment with H8 improved obesity and metabolic disorders, such as insulin resistance and hepatic steatosis by suppressing activity of 11β-HSD1, suggesting that H8 might be a beneficial drug for the treatment of obesity and Type-2 diabetes (T2D).

          Related collections

          Author and article information

          Journal
          Eur. J. Pharmacol.
          European journal of pharmacology
          Elsevier BV
          1879-0712
          0014-2999
          Oct 05 2016
          : 788
          Affiliations
          [1 ] Heilongjiang Key Laboratory of Tissue Damage and Repair, Mudanjiang Medical University, Heilongjiang 157011, PR China.
          [2 ] Institute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, PR China.
          [3 ] Heilongjiang Key Laboratory of Tissue Damage and Repair, Mudanjiang Medical University, Heilongjiang 157011, PR China. Electronic address: yanhui_chu@sina.com.
          [4 ] Institute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, PR China. Electronic address: tydhuang@jnu.edu.cn.
          Article
          S0014-2999(16)30349-1
          10.1016/j.ejphar.2016.05.034
          27242185

          Comments

          Comment on this article