Blockade of Glucocorticoid Excess at the Tissue Level: Inhibitors of 11β-Hydroxysteroid Dehydrogenase Type 1 as a Therapy for Type 2 Diabetes

2008 ◽  
Vol 51 (16) ◽  
pp. 4851-4857 ◽  
Author(s):  
Christopher Fotsch ◽  
Minghan Wang
Keyword(s):  
Type 2 Diabetes ◽  
Hydroxysteroid Dehydrogenase ◽  
Tissue Level

scholarly journals 11?-Hydroxysteroid dehydrogenase Type 1 in obesity and Type 2 diabetes

Diabetologia ◽  
2004 ◽  
Vol 47 (1) ◽  
pp. 1-11 ◽  
Author(s):  
T. M. Stulnig ◽  
W. Waldh�usl
Keyword(s):  
Type 2 Diabetes ◽  
Hydroxysteroid Dehydrogenase

scholarly journals Organ-Based Response to Exercise in Type 1 Diabetes

2012 ◽  
Vol 2012 ◽  
pp. 1-14 ◽  
Author(s):  
Lisa Stehno-Bittel
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Type 1 Diabetes ◽  
Molecular Mechanisms ◽  
Tissue Level ◽  
Significant Research ◽  
Response To Exercise ◽  
Increased Activity

While significant research has clearly identified sedentary behavior as a risk factor for type 2 diabetes and its subsequent complications, the concept that inactivity could be linked to the complications associated with type 1 diabetes (T1D) remains underappreciated. This paper summarizes the known effects of exercise on T1D at the tissue level and focuses on the pancreas, bone, the cardiovascular system, the kidneys, skeletal muscle, and nerves. When possible, the molecular mechanisms underlying the benefits of exercise for T1D are elucidated. The general benefits of increased activity on health and the barriers to increased exercise specific to people with T1D are discussed.

scholarly journals Relationship of 11β-hydroxysteroid dehydrogenase type 1 and hexose-6-phosphate dehydrogenase gene polymorphisms with metabolic syndrome and type 2 diabetes

2011 ◽  
Vol 58 (11) ◽  
pp. 949-959 ◽  
Author(s):  
Seong-Su Moon ◽  
Young-Sil Lee ◽  
Jung-Guk Kim ◽  
Su-Won Kim ◽  
Ji-Yun Jeong ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Metabolic Syndrome ◽  
Gene Polymorphisms ◽  
Hydroxysteroid Dehydrogenase ◽  
Dehydrogenase Gene ◽  
Relationship Of

scholarly journals The 11- -Hydroxysteroid Dehydrogenase Type 1 Inhibitor INCB13739 Improves Hyperglycemia in Patients With Type 2 Diabetes Inadequately Controlled by Metformin Monotherapy

Diabetes Care ◽  
2010 ◽  
Vol 33 (7) ◽  
pp. 1516-1522 ◽  
Author(s):  
J. Rosenstock ◽  
S. Banarer ◽  
V. A. Fonseca ◽  
S. E. Inzucchi ◽  
W. Sun ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Hydroxysteroid Dehydrogenase ◽  
Metformin Monotherapy

scholarly journals Increased Whole-Body and Sustained Liver Cortisol Regeneration by 11β-Hydroxysteroid Dehydrogenase Type 1 in Obese Men With Type 2 Diabetes Provides a Target for Enzyme Inhibition

Diabetes ◽  
2011 ◽  
Vol 60 (3) ◽  
pp. 720-725 ◽  
Author(s):  
Roland H. Stimson ◽  
Ruth Andrew ◽  
Norma C. McAvoy ◽  
Dhiraj Tripathi ◽  
Peter C. Hayes ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Enzyme Inhibition ◽  
Hydroxysteroid Dehydrogenase ◽  
Whole Body

scholarly journals Functional Effects of Polymorphisms in the Human Gene Encoding 11β-Hydroxysteroid Dehydrogenase Type 1 (11β-HSD1): A Sequence Variant at the Translation Start of 11β-HSD1 Alters Enzyme Levels

Endocrinology ◽  
2010 ◽  
Vol 151 (1) ◽  
pp. 195-202 ◽  
Author(s):  
Elise L. V. Malavasi ◽  
Val Kelly ◽  
Nikita Nath ◽  
Alessandra Gambineri ◽  
Rachel S. Dakin ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Hydroxysteroid Dehydrogenase ◽  
In Vitro Translation ◽  
Metabolic Phenotype ◽  
Sequence Variant ◽  
Gene Encoding ◽  
Functional Consequences

Abstract Regeneration of active glucocorticoids within liver and adipose tissue by the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) may be of pathophysiological importance in obesity and metabolic syndrome and is a therapeutic target in type 2 diabetes. Polymorphisms in HSD11B1, the gene encoding 11β-HSD1, have been associated with metabolic phenotype in humans, including type 2 diabetes and hypertension. Here, we have tested the functional consequences of two single nucleotide polymorphisms located in contexts that potentially affect tissue levels of 11β-HSD1. We report no effect of allelic variation at rs846910, a polymorphism within the 5′-flanking region of the gene on HSD11B1 promoter activity in vitro. However, compared with the common G allele, the A allele of rs13306421, a polymorphism located two nucleotides 5′ to the translation initiation site, gave higher 11β-HSD1 expression and activity in vitro and was translated at higher levels in in vitro translation reactions, possibly associated with a lower frequency of “leaky scanning.” These data suggest that this polymorphism may have direct functional consequences on levels of 11β-HSD1 enzyme activity in vivo. However, the rs13306421 A sequence variant originally reported in other ethnic groups may be of low prevalence because it was not detected in a population of 600 European Caucasian women.

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