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

1931-P: Skeletal Muscle (SM) Insulin Resistance (IR) in Coronary Artery Disease (CAD) in Type 1 Diabetes (T1D)

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 1931-P
Author(s):  
KATHERINE V. WILLIAMS ◽  
CHRISTINA M. SHAY ◽  
JULIE PRICE ◽  
TREVOR J. ORCHARD ◽  
DAVID KELLEY
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Coronary Artery Disease ◽  
Type 1 Diabetes ◽  
Coronary Artery ◽  
Artery Disease

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.

scholarly journals Hexose-6-Phosphate Dehydrogenase Contributes to Skeletal Muscle Homeostasis Independent of 11β-Hydroxysteroid Dehydrogenase Type 1

Endocrinology ◽  
2011 ◽  
Vol 152 (1) ◽  
pp. 93-102 ◽  
Author(s):  
Nina M. Semjonous ◽  
Mark Sherlock ◽  
Pancharatnam Jeyasuria ◽  
Keith L. Parker ◽  
Elizabeth A. Walker ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Hydroxysteroid Dehydrogenase ◽  
Muscle Homeostasis

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.

Improvement of insulin sensitivity by antagonism of the renin-angiotensin system

2007 ◽  
Vol 293 (3) ◽  
pp. R974-R980 ◽  
Author(s):  
Erik J. Henriksen
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Glucose Transport ◽  
Renin Angiotensin System ◽  
Whole Body ◽  
Ang Ii ◽  
Angiotensin System ◽  
Skeletal Muscle Insulin Resistance

The reduced capacity of insulin to stimulate glucose transport into skeletal muscle, termed insulin resistance, is a primary defect leading to the development of prediabetes and overt type 2 diabetes. Although the etiology of this skeletal muscle insulin resistance is multifactorial, there is accumulating evidence that one contributor is overactivity of the renin-angiotensin system (RAS). Angiotensin II (ANG II) produced from this system can act on ANG II type 1 receptors both in the vascular endothelium and in myocytes, with an enhancement of the intracellular production of reactive oxygen species (ROS). Evidence from animal model and cultured skeletal muscle cell line studies indicates ANG II can induce insulin resistance. Chronic ANG II infusion into an insulin-sensitive rat produces a markedly insulin-resistant state that is associated with a negative impact of ROS on the skeletal muscle glucose transport system. ANG II treatment of L6 myocytes causes impaired insulin receptor substrate (IRS)-1-dependent insulin signaling that is accompanied by augmentation of NADPH oxidase-mediated ROS production. Further critical evidence has been obtained from the TG(mREN2)27 rat, a model of RAS overactivity and insulin resistance. The TG(mREN2)27 rat displays whole body and skeletal muscle insulin resistance that is associated with local oxidative stress and a significant reduction in the functionality of the insulin receptor (IR)/IRS-1-dependent insulin signaling. Treatment with a selective ANG II type 1 receptor antagonist leads to improvements in whole body insulin sensitivity, enhanced insulin-stimulated glucose transport in muscle, and reduced local oxidative stress. In addition, exercise training of TG(mREN2)27 rats enhances whole body and skeletal muscle insulin action. However, these metabolic improvements elicited by antagonism of ANG II action or exercise training are independent of upregulation of IR/IRS-1-dependent signaling. Collectively, these findings support targeting the RAS in the design of interventions to improve metabolic and cardiovascular function in conditions of insulin resistance associated with prediabetes and type 2 diabetes.

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

Glucocorticoid-mediated effects on metabolism are reversed by targeting 11 beta hydroxysteroid dehydrogenase type 1 in human skeletal muscle

2009 ◽  
Vol 25 (3) ◽  
pp. 250-258 ◽  
Author(s):  
Firoozeh Salehzadeh ◽  
Lubna Al-Khalili ◽  
Sameer S Kulkarni ◽  
Minghan Wang ◽  
Fredrik Lönnqvist ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Human Skeletal Muscle ◽  
Hydroxysteroid Dehydrogenase ◽  
Mediated Effects
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