scholarly journals The Glucose-6-Phosphate Transporter-Hexose-6-Phosphate Dehydrogenase-11β-Hydroxysteroid Dehydrogenase Type 1 System of the Adipose Tissue

Endocrinology ◽  
2007 ◽  
Vol 148 (5) ◽  
pp. 2487-2495 ◽  
Author(s):  
Paola Marcolongo ◽  
Simona Piccirella ◽  
Silvia Senesi ◽  
Livius Wunderlich ◽  
Isabelle Gerin ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Adipose Tissue ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Hydroxysteroid Dehydrogenase ◽  
Phosphate Transporter ◽  
Nicotinamide Adenine ◽  
Functional Connection ◽  
Pharmacological Targets ◽  
Isolated Adipocytes

11β-Hydroxysteroid dehydrogenase type 1, expressed mainly in the endoplasmic reticulum of adipocytes and hepatocytes, plays an important role in the prereceptorial activation of glucocorticoids. In liver endoplasmic reticulum-derived microsomal vesicles, nicotinamide adenine dinucleotide phosphate reduced supply to the enzyme is guaranteed by a tight functional connection with hexose-6-phosphate dehydrogenase and the glucose-6-phosphate transporter (G6PT). In adipose tissue, the proteins and their activities supporting the action of 11β-hydroxysteroid dehydrogenase type 1 have not been explored yet. Here we report the occurrence of the hexose-6-phosphate dehydrogenase in rat epididymal fat, as detected at the level of mRNA, protein, and activity. In the isolated microsomes, the activity was evident only on the permeabilization of the membrane because of the poor permeability to the cofactor nicotinamide adenine dineucleotide phosphate (NADP+), which is consistent with the intralumenal compartmentation of both the enzyme and a pool of pyridine nucleotides. In fat cells, the access of the substrate, glucose-6-phosphate to the intralumenal hexose-6-phosphate dehydrogenase appeared to be mediated by the liver-type G6PT. In fact, the G6PT expression was revealed at the level of mRNA and protein. Accordingly, the transport of glucose-6-phosphate was demonstrated in microsomal vesicles, and it was inhibited by S3483, a prototypic inhibitor of G6PT. Furthermore, isolated adipocytes produced cortisol on addition of cortisone, and the production was markedly inhibited by S3483. The results show that adipocytes are equipped with a functional G6PT-hexose-6-phosphate dehydrogenase-11β-hydroxysteroid dehydrogenase type 1 system and indicate that all three components are potential pharmacological targets for modulating local glucocorticoid activation.

scholarly journals Adipose tissue-targeted 11β-hydroxysteroid dehydrogenase type 1 inhibitor protects against diet-induced obesity

2011 ◽  
Vol 58 (3) ◽  
pp. 199-209 ◽  
Author(s):  
Juan Liu ◽  
Long Wang ◽  
Aisen Zhang ◽  
Wenjuan Di ◽  
Xiao Zhang ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Hydroxysteroid Dehydrogenase ◽  
Diet Induced Obesity

Overexpression of hepatic 5α-reductase and 11β-hydroxysteroid dehydrogenase type 1 in visceral adipose tissue is associated with hyperinsulinemia in morbidly obese patients

Metabolism ◽  
2011 ◽  
Vol 60 (12) ◽  
pp. 1775-1780 ◽  
Author(s):  
René Baudrand ◽  
José Miguel Domínguez ◽  
Cristian A. Carvajal ◽  
Arnoldo Riquelme ◽  
Carmen Campino ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Visceral Adipose Tissue ◽  
Hydroxysteroid Dehydrogenase ◽  
Morbidly Obese ◽  
Obese Patients ◽  
Visceral Adipose

scholarly journals Expression of 11β-Hydroxysteroid Dehydrogenase Type 1 in Adipose Tissue Is Not Increased in Human Obesity

2002 ◽  
Vol 87 (12) ◽  
pp. 5630-5635 ◽  
Author(s):  
J. W. Tomlinson ◽  
B. Sinha ◽  
I. Bujalska ◽  
M. Hewison ◽  
P. M. Stewart
Keyword(s):  
Adipose Tissue ◽  
Hydroxysteroid Dehydrogenase ◽  
Human Obesity

scholarly journals Extra-adrenal regeneration of glucocorticoids by 11β-hydroxysteroid dehydrogenase type 1: physiological regulator and pharmacological target for energy partitioning

2007 ◽  
Vol 66 (1) ◽  
pp. 1-8 ◽  
Author(s):  
Brian R. Walker
Keyword(s):  
Adipose Tissue ◽  
Human Subjects ◽  
Physiological Role ◽  
Hydroxysteroid Dehydrogenase ◽  
Receptor Activation ◽  
Energy Partitioning ◽  
Metabolic Complications ◽  
Cortisol Levels ◽  
Specific Regulation

The major glucocorticoid in man, cortisol, plays important roles in regulating fuel metabolism, energy partitioning and body fat distribution. In addition to the control of cortisol levels in blood by the hypothalamic–pituitary–adrenal axis, intracellular cortisol levels within target tissues can be controlled by local enzymes. 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) catalyses the regeneration of active cortisol from inert cortisone, thereby amplifying cortisol levels and glucocorticoid receptor activation in adipose tissue, liver and other tissues. 11β-HSD1 is under complex tissue-specific regulation and there is evidence that it adjusts local cortisol concentrations independently of the plasma cortisol concentrations, e.g. in response to changes in diet. In obesity 11β-HSD1 mRNA and activity in adipose tissue are increased. The mechanism of this up-regulation remains uncertain; polymorphisms in the HSD11B1 gene have been associated with metabolic complications of obesity, including hypertension and type 2 diabetes, but not with obesity per se. Extensive data have been obtained in mice with transgenic over-expression of 11β-HSD1 in liver and adipocytes, targeted deletion of 11β-HSD1, and using novel selective 11β-HSD1 inhibitors; these data support the use of 11β-HSD1 inhibitors to lower intracellular glucocorticoid levels and treat both obesity and its metabolic complications. Moreover, in human subjects the non-selective ‘prototype’ inhibitor carbenoxolone enhances insulin sensitivity. Results of clinical studies with novel potent selective 11β-HSD1 inhibitors are therefore eagerly awaited. The present article focuses on the physiological role of glucocorticoids in regulating energy partitioning, and the evidence that this process is modulated by 11β-HSD1 in human subjects.

scholarly journals Growth Hormone (GH) Substitution in GH-Deficient Patients Inhibits 11β-Hydroxysteroid Dehydrogenase Type 1 Messenger Ribonucleic Acid Expression in Adipose Tissue

2006 ◽  
Vol 91 (3) ◽  
pp. 1093-1098 ◽  
Author(s):  
Søren Kildeberg Paulsen ◽  
Steen Bønløkke Pedersen ◽  
Jens Otto Lunde Jørgensen ◽  
Sanne Fisker ◽  
Jens Sandahl Christiansen ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Adipose Tissue ◽  
Ribonucleic Acid ◽  
Hydroxysteroid Dehydrogenase ◽  
Messenger Ribonucleic Acid

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.

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