Effect of 11 beta-hydroxysteroid dehydrogenase-1 inhibition on hepatic glucose metabolism in the conscious dog.

Edgerton DS, Basu R, Ramnanan CJ, Farmer TD, Neal D, Scott M, Jacobson P, Rizza RA, Cherrington AD
Am J Physiol Endocrinol Metab. 2010 298 (5): E1019-26

PMID: 20159854 · PMCID: PMC2867371 · DOI:10.1152/ajpendo.00740.2009

Inactive cortisone is converted to active cortisol within the liver by 11 beta-hydroxysteroid dehydrogenase-1 (11 beta-HSD1), and impaired regulation of this process may be related to increased hepatic glucose production (HGP) in individuals with type 2 diabetes. The primary aim of this study was to investigate the effect of acute 11 beta-HSD1 inhibition on HGP and fat metabolism during insulin deficiency. Sixteen conscious, 42-h-fasted, lean, healthy dogs were studied. Somatostatin was infused to create insulin deficiency, and the animals were treated with a specific 11 beta-HSD1 inhibitor (compound 531) or placebo for 5 h. 11 beta-HSD1 inhibition completely suppressed hepatic cortisol production, and this attenuated the increase in HGP that occurred during insulin deficiency. PEPCK and glucose-6-phosphatase expression were decreased when 11 beta-HSD1 was inhibited, but gluconeogenic flux was unchanged, implying an effect on glycogenolysis. Since inhibition of hepatic cortisol production reduces HGP during insulin deficiency, 11 beta-HSD1 is a potential therapeutic target for the treatment of excess glucose production that occurs in diabetes.

MeSH Terms (13)

11-beta-Hydroxysteroid Dehydrogenase Type 1 Analysis of Variance Animals Dogs Female Gluconeogenesis Glucose Hydrocortisone Insulin Liver Male Random Allocation Somatostatin

Connections (3)

This publication is referenced by other Labnodes entities: