scholarly journals Selective Inhibition of 11β-Hydroxysteroid Dehydrogenase Type 1 Improves Hepatic Insulin Sensitivity in Hyperglycemic Mice Strains

Endocrinology ◽  
2003 ◽  
Vol 144 (11) ◽  
pp. 4755-4762 ◽  
Author(s):  
Pēteris Alberts ◽  
Cecilia Nilsson ◽  
Göran Selén ◽  
Lars O. M. Engblom ◽  
Naimie H. M. Edling ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Selective Inhibition ◽  
Hydroxysteroid Dehydrogenase ◽  
Hepatic Insulin Sensitivity

scholarly journals Improved Lipid and Lipoprotein Profile, Hepatic Insulin Sensitivity, and Glucose Tolerance in 11β-Hydroxysteroid Dehydrogenase Type 1 Null Mice

2001 ◽  
Vol 276 (44) ◽  
pp. 41293-41300 ◽  
Author(s):  
Nicholas M. Morton ◽  
Megan C. Holmes ◽  
Catherine Fiévet ◽  
Bart Staels ◽  
Anne Tailleux ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Hydroxysteroid Dehydrogenase ◽  
Lipoprotein Profile ◽  
Hepatic Insulin Sensitivity

scholarly journals Selective Inhibition of Steroidogenic Enzymes by Ketoconazole in Rat Ovary Cells

2014 ◽  
Vol 8 ◽  
pp. CMRH.S14036 ◽  
Author(s):  
Michael Gal ◽  
Joseph Orly
Keyword(s):  
Selective Inhibition ◽  
Hydroxysteroid Dehydrogenase ◽  
Dependent Manner ◽  
Steroidogenic Enzymes ◽  
Ovary Cells ◽  
Estrogen Synthesis ◽  
Lyase Activity ◽  
Testicular Steroidogenesis ◽  
Rat Ovary

Objective Ketoconazole (KCZ) is an anti-fungal agent extensively used for clinical applications related to its inhibitory effects on adrenal and testicular steroidogenesis. Much less information is available on the effects of KCZ on synthesis of steroid hormones in the ovary. The present study aimed to characterize the in situ effects of KCZ on steroidogenic enzymes in primary rat ovary cells. Methods Following the induction of folliculogenesis in gonadotropin treated rats, freshly prepared ovarian cells were incubated in suspension for up to four hours while radiolabeled steroid substrates were added and time dependent generation of their metabolic products was analyzed by thin layer chromatography (TLC). Results KCZ inhibits the P450 steroidogenic enzymes in a selective and dose dependent manner, including cholesterol side-chain cleavage cytochrome P450 (CYP11A1/P450scc), the 17α-hydroxylase activity of CYP17A1/P450c17, and CYP19A1/P450arom, with IC50 values of 0.3, 1.8, and 0.3 μg/mL (0.56, 3.36, and 0.56 μM), respectively. Unaffected by KCZ, at 10 μg/mL, were the 17,20 lyase activity of CYP17A1, as well as five non-cytochrome steroidogenic enzymes including 3β-hydroxysteroid dehydrogenase-δ5-4 isomerase type 1 (3βHSD1), 5α-reductase, 20α-hydroxysteroid dehydrogenase (20α-HSD), 3α-hydroxysteroid dehydrogenase (3α-HSD), and 17β-hydroxysteroid dehydrogenase type 1 (17HSD1). Conclusion These findings map the effects of KCZ on the ovarian pathways of progestin, androgen, and estrogen synthesis. Hence, the drug may have a potential use as an acute and reversible modulator of ovarian steroidogenesis in pathological circumstances.

scholarly journals Liver Fat Content and Hepatic Insulin Sensitivity in Overweight Patients With Type 1 Diabetes

2015 ◽  
Vol 100 (2) ◽  
pp. 607-616 ◽  
Author(s):  
Gemma Llauradó ◽  
Ksenia Sevastianova ◽  
Sanja Sädevirta ◽  
Antti Hakkarainen ◽  
Nina Lundbom ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Insulin Sensitivity ◽  
Fat Content ◽  
Liver Fat ◽  
Liver Fat Content ◽  
Hepatic Insulin Sensitivity

The role and regulation of 11β-hydroxysteroid dehydrogenase type 1 in obesity and the metabolic syndrome

2013 ◽  
Vol 15 (2) ◽  
Author(s):  
Roland H. Stimson ◽  
Brian R. Walker
Keyword(s):  
Metabolic Disease ◽  
Adipose Tissue ◽  
Selective Inhibition ◽  
Hydroxysteroid Dehydrogenase ◽  
The Metabolic Syndrome ◽  
Specific Regulation ◽  
Visceral Adipose ◽  
Subcutaneous Adipose

AbstractThe cortisol regenerating enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) amplifies tissue glucocorticoid levels, particularly in the liver and adipose tissue. The importance of this enzyme in causing metabolic disease was highlighted by transgenic mice which over- or under-expressed 11β-HSD1; consequently, selective 11β-HSD1 inhibitors have been widely developed as novel agents to treat obesity and type 2 diabetes mellitus (T2DM). This review focuses on the importance of 11β-HSD1 in humans which has been more difficult to ascertain. The recent development of a deuterated cortisol tracer has allowed us to quantify in vivo cortisol production by 11β-HSD1. These results have been surprising, as cortisol production rates by 11β-HSD1 are at least equivalent to that of the adrenal glands. The vast majority of this production is by the liver (>90%) with a smaller contribution from subcutaneous adipose tissue and possibly skeletal muscle, but with no detectable production from visceral adipose tissue. This tracer has also allowed us to quantify the tissue-specific regulation of 11β-HSD1 observed in obesity and obesity-associated T2DM, determine the likely basis for this dysregulation, and identify obese patients with T2DM as the group most likely to benefit from selective inhibition of 11β-HSD1. Some of these inhibitors have now reached Phase II clinical development, demonstrating efficacy in the treatment of T2DM. We review these results and discuss whether selective 11β-HSD1 inhibitors are likely to be an important new therapy for metabolic disease.

scholarly journals Selective inhibition of 11β-hydroxysteroid dehydrogenase type 1 decreases blood glucose concentrations in hyperglycaemic mice

Diabetologia ◽  
2002 ◽  
Vol 45 (11) ◽  
pp. 1528-1532 ◽  
Author(s):  
Alberts P. ◽  
Engblom L. ◽  
Edling N. ◽  
Forsgren M. ◽  
Klingström G. ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Selective Inhibition ◽  
Hydroxysteroid Dehydrogenase ◽  
Blood Glucose Concentrations
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