• inhibitors
  • Importantly, 11beta-HSD1 activity appears to be intrinsically linked to all features of the metabolic syndrome, which could at least in animal experiments be modulated by use of synthetic selective inhibitors. (ox.ac.uk)
  • Taken together, it appears that inhibitors against 11beta-HSD1 constitute a promising avenue for novel treatment strategies against the underlying causes of cardiovascular and other metabolic diseases. (ox.ac.uk)
  • Although this strengthens the growing contention that 11β-HSD1 inhibitors are an effective therapeutic treatment for metabolic syndrome through actions in multiple organ systems ( 9 ), any physiological role of β-cell 11β-HSD1, and indeed the potentially pathogenic role ( 5 - 8 ) of elevated 11β-HSD1 in islets in vivo, remains uncertain. (diabetesjournals.org)
  • metabolic syndrome
  • The most robust evidence in support of a pathogenetic role of this enzyme in the development of the metabolic syndrome has been reported in experimental animals, whereas results of human studies are less convincing with several case control and cross-sectional studies showing an association between with 11beta-HSD-1 setpoint and individual features of the metabolic syndrome. (unimi.it)
  • protein
  • Biochemical analysis showed that the 3-hydroxyacyl-CoA dehydrogenase activity of the D-bifunctional protein was completely inactive, whereas the enoyl-CoA hydratase component was active. (steroids-australia.net)
  • Their findings showed that the D-bifunctional protein plays an essential role in the peroxisomal beta-oxidation pathway that cannot be compensated for by the L-specific bifunctional protein. (steroids-australia.net)
  • Heterologous production of 11beta-HSD1, devoid of its N-terminal transmembrane segment, is possible but yields only small amounts of soluble protein. (ox.ac.uk)
  • By co-overexpressing GroEL/ES and adding an 11beta-HSD1 inhibitor during protein synthesis, we have increased the accumulation of soluble 11beta-HSD1 by more than one order of magnitude. (ox.ac.uk)
  • Moreover, active site titration of human 11beta-HSD1 revealed that at least 75% of the protein in a typical preparation represents active enzyme. (ox.ac.uk)
  • DHRS7B is a member of the short chain dehydrogenase/reductase (SDR) superfamily and possesses characteristic features of an SDR within the protein sequence. (wikipedia.org)
  • liver
  • This premise is strongly supported by the phenotype of transgenic mice overexpressing 11β-HSD1 in fat or liver, which recapitulates diabetes and insulin-resistant metabolic disease, and by the protection from metabolic disease exhibited by 11β-HSD1 −/− mice ( 3 ). (diabetesjournals.org)
  • human
  • Using monodispersity as a screening criterion, we have also optimized the purification process by evaluating various solubilizing systems for the chromatographic steps, finally obtaining stable monodisperse preparations of both human and guinea pig 11beta-HSD1. (ox.ac.uk)
  • vivo
  • This study investigated a novel approach to estimating 11 beta HSD activity in vivo. (stoynev.us)
  • It may therefore be applied to the measurement of 11 beta HSD activity in vivo in large numbers of hypertensive patients without the use of radioisotopes. (stoynev.us)
  • To test the hypothesis that increased β-cell 11β-HSD1 is diabetogenic, we used the insulin-I promoter ( 10 ) to drive β-cell-specific 11β-HSD1 elevation in vivo in C57Bl/KsJ mice, a strain prone to high-fat (HF) diet-induced β-cell failure ( 11 ). (diabetesjournals.org)
  • To gain insight into potentially relevant miRNAs in vivo, we investigated 2 models with differential 11β-HSD2 activity linked with salt-sensitive hypertension. (ahajournals.org)
  • novel
  • Optimal elevation of β-cell 11β-HSD1 represents a novel biological mechanism supporting compensatory insulin hypersecretion rather than exacerbating metabolic disease. (diabetesjournals.org)
  • known
  • Roxibolone (INN) (developmental code name BR-906), also known as 11β,17β-dihydroxy-17α-methyl-3-oxoandrosta-1,4-diene-2-carboxylic acid, is a steroidal antiglucocorticoid described as an anticholesterolemic (cholesterol-lowering) and anabolic drug which was never marketed. (wikipedia.org)
  • obese
  • Elevated 11β-HSD1 is also found in pancreatic islets of obese/diabetic rodents and is hypothesized to suppress insulin secretion and promote diabetes. (diabetesjournals.org)
  • Salicylate downregulates 11β-HSD1 expression in adipose tissue in obese mice and hence may explain why aspirin improves glycemic control in type 2 diabetes. (wikipedia.org)
  • mice
  • To define the direct impact of elevated pancreatic β-cell 11β-HSD1 on insulin secretion, we generated β-cell-specific, 11β-HSD1-overexpressing (MIP-HSD1) mice on a strain background prone to β-cell failure. (diabetesjournals.org)
  • 11β-HSD1 −/− mice showed mild β-cell impairment that was offset by improved glucose tolerance. (diabetesjournals.org)
  • The benefit of higher β-cell 11β-HSD1 exhibited a threshold because homozygous MIP-HSD1 tg/tg mice and diabetic Lep db/db mice with markedly elevated β-cell 11β-HSD1 levels had impaired basal β-cell function. (diabetesjournals.org)
  • found
  • Here we show that the soluble portion of recombinant 11beta-HSD1 produced in E. coli is found mainly as multimeric aggregates in the absence of detergent, and to a large extent associated with the endogenous chaperonin GroEL and other E. coli proteins. (ox.ac.uk)
  • 11β-HSD1 is also found in pancreatic islets ( 4 ). (diabetesjournals.org)
  • alpha
  • According to sequence similarities at the nucleotide and amino acid levels, the gap junction proteins are divided into two categories, alpha and beta. (genecards.org)