Effect of 11 beta-hydroxysteroid dehydrogenase-1 inhibition on hepatic glucose metabolism in the conscious dog. 2010

Dale S Edgerton, and Rita Basu, and Christopher J Ramnanan, and Tiffany D Farmer, and Doss Neal, and Melanie Scott, and Peer Jacobson, and Robert A Rizza, and Alan D Cherrington
Molecular Physiology and Biophysics, Vanderbilt University Medical Center, 710 Robinson Research Bldg., Nashville, TN 37232-0615, USA. dale.edgerton@vanderbilt.edu

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.

UI MeSH Term Description Entries
D007328 Insulin A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1). Iletin,Insulin A Chain,Insulin B Chain,Insulin, Regular,Novolin,Sodium Insulin,Soluble Insulin,Chain, Insulin B,Insulin, Sodium,Insulin, Soluble,Regular Insulin
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008297 Male Males
D011897 Random Allocation A process involving chance used in therapeutic trials or other research endeavor for allocating experimental subjects, human or animal, between treatment and control groups, or among treatment groups. It may also apply to experiments on inanimate objects. Randomization,Allocation, Random
D004285 Dogs The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065) Canis familiaris,Dog
D005260 Female Females
D005943 Gluconeogenesis Biosynthesis of GLUCOSE from nonhexose or non-carbohydrate precursors, such as LACTATE; PYRUVATE; ALANINE; and GLYCEROL.
D005947 Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Dextrose,Anhydrous Dextrose,D-Glucose,Glucose Monohydrate,Glucose, (DL)-Isomer,Glucose, (alpha-D)-Isomer,Glucose, (beta-D)-Isomer,D Glucose,Dextrose, Anhydrous,Monohydrate, Glucose
D006854 Hydrocortisone The main glucocorticoid secreted by the ADRENAL CORTEX. Its synthetic counterpart is used, either as an injection or topically, in the treatment of inflammation, allergy, collagen diseases, asthma, adrenocortical deficiency, shock, and some neoplastic conditions. Cortef,Cortisol,Pregn-4-ene-3,20-dione, 11,17,21-trihydroxy-, (11beta)-,11-Epicortisol,Cortifair,Cortril,Epicortisol,Hydrocortisone, (11 alpha)-Isomer,Hydrocortisone, (9 beta,10 alpha,11 alpha)-Isomer,11 Epicortisol
D000704 Analysis of Variance A statistical technique that isolates and assesses the contributions of categorical independent variables to variation in the mean of a continuous dependent variable. ANOVA,Analysis, Variance,Variance Analysis,Analyses, Variance,Variance Analyses

Related Publications

Dale S Edgerton, and Rita Basu, and Christopher J Ramnanan, and Tiffany D Farmer, and Doss Neal, and Melanie Scott, and Peer Jacobson, and Robert A Rizza, and Alan D Cherrington
December 2009, Journal of physiology and biochemistry,
Dale S Edgerton, and Rita Basu, and Christopher J Ramnanan, and Tiffany D Farmer, and Doss Neal, and Melanie Scott, and Peer Jacobson, and Robert A Rizza, and Alan D Cherrington
October 1990, Kidney international,
Dale S Edgerton, and Rita Basu, and Christopher J Ramnanan, and Tiffany D Farmer, and Doss Neal, and Melanie Scott, and Peer Jacobson, and Robert A Rizza, and Alan D Cherrington
November 2003, Endocrinology,
Dale S Edgerton, and Rita Basu, and Christopher J Ramnanan, and Tiffany D Farmer, and Doss Neal, and Melanie Scott, and Peer Jacobson, and Robert A Rizza, and Alan D Cherrington
January 1999, Vitamins and hormones,
Dale S Edgerton, and Rita Basu, and Christopher J Ramnanan, and Tiffany D Farmer, and Doss Neal, and Melanie Scott, and Peer Jacobson, and Robert A Rizza, and Alan D Cherrington
April 1994, Bailliere's clinical endocrinology and metabolism,
Dale S Edgerton, and Rita Basu, and Christopher J Ramnanan, and Tiffany D Farmer, and Doss Neal, and Melanie Scott, and Peer Jacobson, and Robert A Rizza, and Alan D Cherrington
January 1993, Vitamins and hormones,
Dale S Edgerton, and Rita Basu, and Christopher J Ramnanan, and Tiffany D Farmer, and Doss Neal, and Melanie Scott, and Peer Jacobson, and Robert A Rizza, and Alan D Cherrington
October 1998, Sheng li ke xue jin zhan [Progress in physiology],
Dale S Edgerton, and Rita Basu, and Christopher J Ramnanan, and Tiffany D Farmer, and Doss Neal, and Melanie Scott, and Peer Jacobson, and Robert A Rizza, and Alan D Cherrington
July 2013, American journal of physiology. Endocrinology and metabolism,
Dale S Edgerton, and Rita Basu, and Christopher J Ramnanan, and Tiffany D Farmer, and Doss Neal, and Melanie Scott, and Peer Jacobson, and Robert A Rizza, and Alan D Cherrington
January 1993, Ryoikibetsu shokogun shirizu,
Dale S Edgerton, and Rita Basu, and Christopher J Ramnanan, and Tiffany D Farmer, and Doss Neal, and Melanie Scott, and Peer Jacobson, and Robert A Rizza, and Alan D Cherrington
February 2000, Nihon rinsho. Japanese journal of clinical medicine,
Copied contents to your clipboard!