Suppression of 11beta-hydroxysteroid dehydrogenase type 1 activity diminish insulin resistance and hypertriglyceridemia in metabolic syndrome

2010 ◽  
Vol 34 (8) ◽  
pp. S30-S30
Author(s):  
Jianqi Cui ◽  
Christine G. Schnackenberg ◽  
Melissa H. Costell ◽  
Daniel J. Krosky ◽  
Charlene W. Wu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Hydroxysteroid Dehydrogenase

Hexose-6-phosphate dehydrogenase in the endoplasmic reticulum

2010 ◽  
Vol 391 (1) ◽  
Author(s):  
Silvia Senesi ◽  
Miklos Csala ◽  
Paola Marcolongo ◽  
Rosella Fulceri ◽  
Jozsef Mandl ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Endoplasmic Reticulum ◽  
Pentose Phosphate Pathway ◽  
Hydroxysteroid Dehydrogenase ◽  
Pyridine Nucleotide ◽  
Pentose Phosphate ◽  
The Metabolic Syndrome ◽  
Glucose 6 Phosphate Dehydrogenase

Abstract Hexose-6-phosphate dehydrogenase (H6PD) is a luminal enzyme of the endoplasmic reticulum that is distinguished from cytosolic glucose-6-phosphate dehydrogenase by several features. H6PD converts glucose-6-phosphate and NADP+ to 6-phosphogluconate and NADPH, thereby catalyzing the first two reactions of the pentose-phosphate pathway. Because the endoplasmic reticulum has a separate pyridine nucleotide pool, H6PD provides NADPH for luminal reductases. One of these enzymes, 11β-hydroxysteroid dehydrogenase type 1 responsible for prereceptorial activation of glucocorticoids, has been the focus of much attention as a probable factor in the pathomechanism of several human diseases including insulin resistance and the metabolic syndrome. This review summarizes recent advances related to the functions of H6PD.

scholarly journals Chronic Inhibition of 11β-Hydroxysteroid Dehydrogenase Type 1 Activity Decreases Hypertension, Insulin Resistance, and Hypertriglyceridemia in Metabolic Syndrome

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Christine G. Schnackenberg ◽  
Melissa H. Costell ◽  
Daniel J. Krosky ◽  
Jianqi Cui ◽  
Charlene W. Wu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Adipose Tissue ◽  
Glucose Intolerance ◽  
Body Weight Gain ◽  
Plasma Renin ◽  
Hydroxysteroid Dehydrogenase ◽  
Common Mechanism ◽  
Metabolic Activities

Metabolic syndrome is a constellation of risk factors including hypertension, dyslipidemia, insulin resistance, and obesity that promote the development of cardiovascular disease. Metabolic syndrome has been associated with changes in the secretion or metabolism of glucocorticoids, which have important functions in adipose, liver, kidney, and vasculature. Tissue concentrations of the active glucocorticoid cortisol are controlled by the conversion of cortisone to cortisol by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). Because of the various cardiovascular and metabolic activities of glucocorticoids, we tested the hypothesis that 11β-HSD1 is a common mechanism in the hypertension, dyslipidemia, and insulin resistance in metabolic syndrome. In obese and lean SHR/NDmcr-cp (SHR-cp), cardiovascular, metabolic, and renal functions were measured before and during four weeks of administration of vehicle or compound 11 (10 mg/kg/d), a selective inhibitor of 11β-HSD1. Compound 11 significantly decreased 11β-HSD1 activity in adipose tissue and liver of SHR-cp. In obese SHR-cp, compound 11 significantly decreased mean arterial pressure, glucose intolerance, insulin resistance, hypertriglyceridemia, and plasma renin activity with no effect on heart rate, body weight gain, or microalbuminuria. These results suggest that 11β-HSD1 activity in liver and adipose tissue is a common mediator of hypertension, hypertriglyceridemia, glucose intolerance, and insulin resistance in metabolic syndrome.

Up-Regulation of mRNA Levels of 11β-Hydroxysteroid Dehydrogenase Type 1 in the Liver of Morbidly Obese Patients with Metabolic Syndrome

2011 ◽  
pp. P2-583-P2-583
Author(s):  
Esther Torrecilla-Garcia ◽  
Gumersindo Fernandez-Vazquez ◽  
David Vicent-Lopez ◽  
Franco Sanchez-Franco ◽  
Lucio Cabrerizo-Garcia ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Hydroxysteroid Dehydrogenase ◽  
Morbidly Obese ◽  
Mrna Levels ◽  
Obese Patients

scholarly journals Increased Nitro-Oxidative Toxicity in Association With Metabolic Syndrome, Atherogenicity and Insulin Resistance in Patients With Affective Disorders

2021 ◽  
Author(s):  
Nayara Morelli ◽  
Michael Maes ◽  
Kamila Bonifacio ◽  
Heber Vargas ◽  
Sandra Nunes ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Mood Disorders ◽  
Lipid Hydroperoxides ◽  
Superoxide Dismutase 1 ◽  
Bipolar Type ◽  
Male Sex ◽  
Nitric Oxide Metabolites ◽  
Composite Scores

Background: There is a strong comorbidity between mood disorders and metabolic syndrome (MetS). Increased levels of reactive oxygen and nitrogen species (RONS) and nitro-oxidative stress toxicity (NOSTOX) partially underpin this comorbidity.Aims: To examine the associations of RONS/NOSTOX biomarkers with MetS after adjusting for the significant effects of mood disorders (major depression, and bipolar type 1 and 2), generalized anxiety disorder (GAD), tobacco use disorder (TUD), and male sex.Methods: The study included subjects with (n=65) and without (n=107) MetS and measured levels of superoxide dismutase 1 (SOD1), lipid hydroperoxides (LOOH), nitric oxide metabolites (NOx), malondialdehyde (MDA), and advanced oxidation protein products (AOPP) and computed z unit-weighted composite scores which reflect RONS/NOSTOX. The study included 105 patients with mood disorders, 46 with GAD, and 95 with TUD.Results: MetS was associated with increased levels of MDA and AOPP, independently from mood disorders, TUD, sex and GAD. Atherogenicity and insulin resistance (IR) were significantly associated with a NOSTOX composite score. Mood disorders, TUD, GAD, male sex and MetS independently contribute to increased RONS/NOSTOX. The RONS/NOSTOX profile of MetS was different from that of GAD, which showed increased SOD1 and NOx levels. TUD was accompanied by increased SOD1, LOOH and MDA, and male sex by increased LOOH and AOPP.Conclusions: MetS is characterized by increased lipid peroxidation with aldehyde formation and chlorinative stress, and atherogenicity and IR are strongly mediated by RONS/NOSTOX. Partially shared RONS/NOSTOX pathways underpin the comorbidity of MetS with mood disorders, GAD, and TUD.

scholarly journals 11 -Hydroxysteroid Dehydrogenase Type 1 Regulates Glucocorticoid-Induced Insulin Resistance in Skeletal Muscle

Diabetes ◽  
2009 ◽  
Vol 58 (11) ◽  
pp. 2506-2515 ◽  
Author(s):  
S. A. Morgan ◽  
M. Sherlock ◽  
L. L. Gathercole ◽  
G. G. Lavery ◽  
C. Lenaghan ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Hydroxysteroid Dehydrogenase

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

2016 ◽  
Vol 788 ◽  
pp. 140-151 ◽  
Author(s):  
Xiaohuan Yuan ◽  
Hongzhi Li ◽  
He Bai ◽  
Xiaojin Zhao ◽  
Chunlei Zhang ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Hepatic Steatosis ◽  
Hydroxysteroid Dehydrogenase

scholarly journals Elevated hepatic 11β-hydroxysteroid dehydrogenase type 1 induces insulin resistance in uremia

2014 ◽  
Vol 111 (10) ◽  
pp. 3817-3822 ◽  
Author(s):  
Ananda Chapagain ◽  
Paul W. Caton ◽  
Julius Kieswich ◽  
Petros Andrikopoulos ◽  
Nanda Nayuni ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Signaling ◽  
Hydroxysteroid Dehydrogenase ◽  
Metabolic Disturbances ◽  
Intracellular Regeneration ◽  
Rat Models ◽  
Hepatic Expression ◽  
Lipogenic Genes ◽  
Subtotal Nephrectomy

Insulin resistance and associated metabolic sequelae are common in chronic kidney disease (CKD) and are positively and independently associated with increased cardiovascular mortality. However, the pathogenesis has yet to be fully elucidated. 11β-Hydroxysteroid dehydrogenase type 1 (11βHSD1) catalyzes intracellular regeneration of active glucocorticoids, promoting insulin resistance in liver and other metabolic tissues. Using two experimental rat models of CKD (subtotal nephrectomy and adenine diet) which show early insulin resistance, we found that 11βHSD1 mRNA and protein increase in hepatic and adipose tissue, together with increased hepatic 11βHSD1 activity. This was associated with intrahepatic but not circulating glucocorticoid excess, and increased hepatic gluconeogenesis and lipogenesis. Oral administration of the 11βHSD inhibitor carbenoxolone to uremic rats for 2 wk improved glucose tolerance and insulin sensitivity, improved insulin signaling, and reduced hepatic expression of gluconeogenic and lipogenic genes. Furthermore, 11βHSD1−/− mice and rats treated with a specific 11βHSD1 inhibitor (UE2316) were protected from metabolic disturbances despite similar renal dysfunction following adenine experimental uremia. Therefore, we demonstrate that elevated hepatic 11βHSD1 is an important contributor to early insulin resistance and dyslipidemia in uremia. Specific 11βHSD1 inhibitors potentially represent a novel therapeutic approach for management of insulin resistance in patients with CKD.

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