Inhibition of 11β-hydroxysteroid dehydrogenase type 1 ameliorates obesity-related insulin resistance

2016 ◽  
Vol 478 (1) ◽  
pp. 474-480 ◽  
Author(s):  
Shiying Shao ◽  
Xiaojie Zhang ◽  
Muxun Zhang
Keyword(s):  
Insulin Resistance ◽  
Hydroxysteroid Dehydrogenase

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.

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 Ectopic lipid deposition mediates insulin resistance in adipose specific 11β-hydroxysteroid dehydrogenase type 1 transgenic mice

Metabolism ◽  
2019 ◽  
Vol 93 ◽  
pp. 1-9 ◽  
Author(s):  
Abudukadier Abulizi ◽  
João-Paulo Camporez ◽  
Dongyan Zhang ◽  
Varman T. Samuel ◽  
Gerald I. Shulman ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Transgenic Mice ◽  
Hydroxysteroid Dehydrogenase ◽  
Lipid Deposition

11β-Hydroxysteroid Dehydrogenase Type 1 in Adipose Tissue and Prospective Changes in Body Weight and Insulin Resistance*

Obesity ◽  
2006 ◽  
Vol 14 (9) ◽  
pp. 1515-1522 ◽  
Author(s):  
Juraj Koska ◽  
Barbora de Courten ◽  
Deborah J. Wake ◽  
Saraswathy Nair ◽  
Brian R. Walker ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Body Weight ◽  
Adipose Tissue ◽  
Hydroxysteroid Dehydrogenase

scholarly journals 11β-Hydroxysteroid Dehydrogenase Type 1(11β-HSD1) mediates insulin resistance through JNK activation in adipocytes

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Kesong Peng ◽  
Yong Pan ◽  
Jieli Li ◽  
Zia Khan ◽  
Mendi Fan ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Hydroxysteroid Dehydrogenase ◽  
Jnk Activation

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

scholarly journals 11β-Hydroxysteroid dehydrogenase type 1 shRNA ameliorates glucocorticoid-induced insulin resistance and lipolysis in mouse abdominal adipose tissue

2015 ◽  
Vol 308 (1) ◽  
pp. E84-E95 ◽  
Author(s):  
Ying Wang ◽  
Chaoying Yan ◽  
Limei Liu ◽  
Wei Wang ◽  
Hanze Du ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Insulin Signaling ◽  
Hydroxysteroid Dehydrogenase ◽  
Target Tissue ◽  
The Metabolic Syndrome ◽  
Lipid Metabolism Genes

Long-term glucocorticoid exposure increases the risk for developing type 2 diabetes. Prereceptor activation of glucocorticoid availability in target tissue by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) coupled with hexose-6-phosphate dehydrogenase (H6PDH) is an important mediator of the metabolic syndrome. We explored whether the tissue-specific modulation of 11β-HSD1 and H6PDH in adipose tissue mediates glucocorticoid-induced insulin resistance and lipolysis and analyzed the effects of 11β-HSD1 inhibition on the key lipid metabolism genes and insulin-signaling cascade. We observed that corticosterone (CORT) treatment increased expression of 11β-HSD1 and H6PDH and induced lipase HSL and ATGL with suppression of p-Thr172 AMPK in adipose tissue of C57BL/6J mice. In contrast, CORT induced adipose insulin resistance, as reflected by a marked decrease in IR and IRS-1 gene expression with a reduction in p-Thr308 Akt/PKB. Furthermore, 11β-HSD1 shRNA attenuated CORT-induced 11β-HSD1 and lipase expression and improved insulin sensitivity with a concomitant stimulation of pThr308 Akt/PKB and p-Thr172 AMPK within adipose tissue. Addition of CORT to 3T3-L1 adipocytes enhanced 11β-HSD1 and H6PDH and impaired p-Thr308 Akt/PKB, leading to lipolysis. Knockdown of 11β-HSD1 by shRNA attenuated CORT-induced lipolysis and reversed CORT-mediated inhibition of pThr172 AMPK, which was accompanied by a parallel improvement of insulin signaling response in these cells. These findings suggest that elevated adipose 11β-HSD1 expression may contribute to glucocorticoid-induced insulin resistance and adipolysis.

Sign in / Sign up

Export Citation Format

Share Document