Hydroxysteroid Dehydrogenases: Enzymes of the oxidoreductase class that catalyze the dehydrogenation of hydroxysteroids. (From Enzyme Nomenclature, 1992) EC 1.1.-.11-beta-Hydroxysteroid Dehydrogenase Type 1: A low-affinity 11 beta-hydroxysteroid dehydrogenase found in a variety of tissues, most notably in LIVER; LUNG; ADIPOSE TISSUE; vascular tissue; OVARY; and the CENTRAL NERVOUS SYSTEM. The enzyme acts reversibly and can use either NAD or NADP as cofactors.11-beta-Hydroxysteroid Dehydrogenase Type 2: An high-affinity, NAD-dependent 11-beta-hydroxysteroid dehydrogenase that acts unidirectionally to catalyze the dehydrogenation of CORTISOL to CORTISONE. It is found predominantly in mineralocorticoid target tissues such as the KIDNEY; COLON; SWEAT GLANDS; and the PLACENTA. Absence of the enzyme leads to a fatal form of childhood hypertension termed, APPARENT MINERALOCORTICOID EXCESS SYNDROME.17-Hydroxysteroid Dehydrogenases: A class of enzymes that catalyzes the oxidation of 17-hydroxysteroids to 17-ketosteroids. EC 1.1.-.3-Hydroxysteroid Dehydrogenases: Catalyze the oxidation of 3-hydroxysteroids to 3-ketosteroids.11-beta-Hydroxysteroid Dehydrogenases: Hydroxysteroid dehydrogenases that catalyzes the reversible conversion of CORTISOL to the inactive metabolite CORTISONE. Enzymes in this class can utilize either NAD or NADP as cofactors.20-Hydroxysteroid Dehydrogenases: A group of enzymes that catalyze the reversible reduction-oxidation reaction of 20-hydroxysteroids, such as from a 20-ketosteroid to a 20-alpha-hydroxysteroid (EC 1.1.1.149) or to a 20-beta-hydroxysteroid (EC 1.1.1.53).Steroid 17-alpha-Hydroxylase: A microsomal cytochrome P450 enzyme that catalyzes the 17-alpha-hydroxylation of progesterone or pregnenolone and subsequent cleavage of the residual two carbons at C17 in the presence of molecular oxygen and NADPH-FERRIHEMOPROTEIN REDUCTASE. This enzyme, encoded by CYP17 gene, generates precursors for glucocorticoid, androgen, and estrogen synthesis. Defects in CYP17 gene cause congenital adrenal hyperplasia (ADRENAL HYPERPLASIA, CONGENITAL) and abnormal sexual differentiation.3-alpha-Hydroxysteroid Dehydrogenase (B-Specific): A 3-hydroxysteroid dehydrogenase which catalyzes the reversible reduction of the active androgen, DIHYDROTESTOSTERONE to 5 ALPHA-ANDROSTANE-3 ALPHA,17 BETA-DIOL. It also has activity towards other 3-alpha-hydroxysteroids and on 9-, 11- and 15- hydroxyprostaglandins. The enzyme is B-specific in reference to the orientation of reduced NAD or NADPH.Hydrocortisone: The main glucocorticoid secreted by the ADRENAL CORTEX. Its synthetic counterpart is used, either as an injection or topically, in the treatment of inflammation, allergy, collagen diseases, asthma, adrenocortical deficiency, shock, and some neoplastic conditions.Estradiol Dehydrogenases: Enzymes that catalyze the oxidation of estradiol at the 17-hydroxyl group in the presence of NAD+ or NADP+ to yield estrone and NADH or NADPH. The 17-hydroxyl group can be in the alpha- or beta-configuration. EC 1.1.1.62Cortisone: A naturally occurring glucocorticoid. It has been used in replacement therapy for adrenal insufficiency and as an anti-inflammatory agent. Cortisone itself is inactive. It is converted in the liver to the active metabolite HYDROCORTISONE. (From Martindale, The Extra Pharmacopoeia, 30th ed, p726)Sulfotransferases: Enzymes which transfer sulfate groups to various acceptor molecules. They are involved in posttranslational sulfation of proteins and sulfate conjugation of exogenous chemicals and bile acids. EC 2.8.2.Alcohol Oxidoreductases: A subclass of enzymes which includes all dehydrogenases acting on primary and secondary alcohols as well as hemiacetals. They are further classified according to the acceptor which can be NAD+ or NADP+ (subclass 1.1.1), cytochrome (1.1.2), oxygen (1.1.3), quinone (1.1.5), or another acceptor (1.1.99).Steroids: A group of polycyclic compounds closely related biochemically to TERPENES. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (STEROLS), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. (From Hawley's Condensed Chemical Dictionary, 11th ed)NAD: A coenzyme composed of ribosylnicotinamide 5'-diphosphate coupled to adenosine 5'-phosphate by pyrophosphate linkage. It is found widely in nature and is involved in numerous enzymatic reactions in which it serves as an electron carrier by being alternately oxidized (NAD+) and reduced (NADH). (Dorland, 27th ed)Carbohydrate Dehydrogenases: Reversibly catalyze the oxidation of a hydroxyl group of carbohydrates to form a keto sugar, aldehyde or lactone. Any acceptor except molecular oxygen is permitted. Includes EC 1.1.1.; EC 1.1.2.; and 1.1.99.Kinetics: The rate dynamics in chemical or physical systems.Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.Testosterone: A potent androgenic steroid and major product secreted by the LEYDIG CELLS of the TESTIS. Its production is stimulated by LUTEINIZING HORMONE from the PITUITARY GLAND. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to DIHYDROTESTOSTERONE or ESTRADIOL.L-Lactate Dehydrogenase: A tetrameric enzyme that, along with the coenzyme NAD+, catalyzes the interconversion of LACTATE and PYRUVATE. In vertebrates, genes for three different subunits (LDH-A, LDH-B and LDH-C) exist.Androsterone: A metabolite of TESTOSTERONE or ANDROSTENEDIONE with a 3-alpha-hydroxyl group and without the double bond. The 3-beta hydroxyl isomer is epiandrosterone.Alcohol Dehydrogenase: A zinc-containing enzyme which oxidizes primary and secondary alcohols or hemiacetals in the presence of NAD. In alcoholic fermentation, it catalyzes the final step of reducing an aldehyde to an alcohol in the presence of NADH and hydrogen.TetrahydrocortisolAntineoplastic Protocols: Clinical protocols used to inhibit the growth or spread of NEOPLASMS.TetrahydrocortisoneGlyceraldehyde-3-Phosphate Dehydrogenases: Enzymes that catalyze the dehydrogenation of GLYCERALDEHYDE 3-PHOSPHATE. Several types of glyceraldehyde-3-phosphate-dehydrogenase exist including phosphorylating and non-phosphorylating varieties and ones that transfer hydrogen to NADP and ones that transfer hydrogen to NAD.Carbenoxolone: An agent derived from licorice root. It is used for the treatment of digestive tract ulcers, especially in the stomach. Antidiuretic side effects are frequent, but otherwise the drug is low in toxicity.Receptors, Mineralocorticoid: Cytoplasmic proteins that specifically bind MINERALOCORTICOIDS and mediate their cellular effects. The receptor with its bound ligand acts in the nucleus to induce transcription of specific segments of DNA.20-alpha-Hydroxysteroid Dehydrogenase: An enzymes that catalyzes the reversible reduction-oxidation reaction of 20-alpha-hydroxysteroids, such as from PROGESTERONE to 20-ALPHA-DIHYDROPROGESTERONE.IMP Dehydrogenase: An enzyme that catalyzes the dehydrogenation of inosine 5'-phosphate to xanthosine 5'-phosphate in the presence of NAD. EC 1.1.1.205.Drug Design: The molecular designing of drugs for specific purposes (such as DNA-binding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include pharmacokinetics, dosage analysis, or drug administration analysis.Glucocorticoids: A group of CORTICOSTEROIDS that affect carbohydrate metabolism (GLUCONEOGENESIS, liver glycogen deposition, elevation of BLOOD SUGAR), inhibit ADRENOCORTICOTROPIC HORMONE secretion, and possess pronounced anti-inflammatory activity. They also play a role in fat and protein metabolism, maintenance of arterial blood pressure, alteration of the connective tissue response to injury, reduction in the number of circulating lymphocytes, and functioning of the central nervous system.Mineralocorticoid Excess Syndrome, Apparent: A hereditary disease characterized by childhood onset HYPERTENSION, hypokalemic alkalosis, and low RENIN and ALDOSTERONE secretion. It results from a defect in the activity of the 11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE 2 enzyme which results in inadequate conversion of CORTISOL to CORTISONE. The build up of unprocessed cortisol to levels that stimulate MINERALOCORTICOID RECEPTORS creates the appearance of having excessive MINERALOCORTICOIDS.Mineralocorticoids: A group of CORTICOSTEROIDS primarily associated with water and electrolyte balance. This is accomplished through the effect on ION TRANSPORT in renal tubules, resulting in retention of sodium and loss of potassium. Mineralocorticoid secretion is itself regulated by PLASMA VOLUME, serum potassium, and ANGIOTENSIN II.Metabolic Syndrome X: A cluster of metabolic risk factors for CARDIOVASCULAR DISEASES and TYPE 2 DIABETES MELLITUS. The major components of metabolic syndrome X include excess ABDOMINAL FAT; atherogenic DYSLIPIDEMIA; HYPERTENSION; HYPERGLYCEMIA; INSULIN RESISTANCE; a proinflammatory state; and a prothrombotic (THROMBOSIS) state. (from AHA/NHLBI/ADA Conference Proceedings, Circulation 2004; 109:551-556)PubMed: A bibliographic database that includes MEDLINE as its primary subset. It is produced by the National Center for Biotechnology Information (NCBI), part of the NATIONAL LIBRARY OF MEDICINE. PubMed, which is searchable through NLM's Web site, also includes access to additional citations to selected life sciences journals not in MEDLINE, and links to other resources such as the full-text of articles at participating publishers' Web sites, NCBI's molecular biology databases, and PubMed Central.Periodicals as Topic: A publication issued at stated, more or less regular, intervals.BooksPublishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing.MEDLINE: The premier bibliographic database of the NATIONAL LIBRARY OF MEDICINE. MEDLINE® (MEDLARS Online) is the primary subset of PUBMED and can be searched on NLM's Web site in PubMed or the NLM Gateway. MEDLINE references are indexed with MEDICAL SUBJECT HEADINGS (MeSH).Serial Publications: Publications in any medium issued in successive parts bearing numerical or chronological designations and intended to be continued indefinitely. (ALA Glossary of Library and Information Science, 1983, p203)Biological Science Disciplines: All of the divisions of the natural sciences dealing with the various aspects of the phenomena of life and vital processes. The concept includes anatomy and physiology, biochemistry and biophysics, and the biology of animals, plants, and microorganisms. It should be differentiated from BIOLOGY, one of its subdivisions, concerned specifically with the origin and life processes of living organisms.Insulin Resistance: Diminished effectiveness of INSULIN in lowering blood sugar levels: requiring the use of 200 units or more of insulin per day to prevent HYPERGLYCEMIA or KETOSIS.Insulin: A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1).Glucose: A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement.Endocrinology: A subspecialty of internal medicine concerned with the metabolism, physiology, and disorders of the ENDOCRINE SYSTEM.Dexamethasone: An anti-inflammatory 9-fluoro-glucocorticoid.Glucose Clamp Technique: Maintenance of a constant blood glucose level by perfusion or infusion with glucose or insulin. It is used for the study of metabolic rates (e.g., in glucose, lipid, amino acid metabolism) at constant glucose concentration.Muscle, Skeletal: A subtype of striated muscle, attached by TENDONS to the SKELETON. Skeletal muscles are innervated and their movement can be consciously controlled. They are also called voluntary muscles.Patents as Topic: Exclusive legal rights or privileges applied to inventions, plants, etc.Nucleoside Q: A modified nucleoside which is present in the first position of the anticodon of tRNA-tyrosine, tRNA-histidine, tRNA-asparagine and tRNA-aspartic acid of many organisms. It is believed to play a role in the regulatory function of tRNA. Nucleoside Q can be further modified to nucleoside Q*, which has a mannose or galactose moiety linked to position 4 of its cyclopentenediol moiety.Inventions: A novel composition, device, or process, independently conceived de novo or derived from a pre-existing model.Androstanes: The family of steroids from which the androgens are derived.Oxidoreductases, O-Demethylating: Drug metabolizing enzymes which oxidize methyl ethers. Usually found in liver microsomes.Lawyers: Persons whose profession is to give legal advice and assistance to clients and represent them in legal matters. (American Heritage Dictionary, 3d ed)
High dietary potassium chloride intake augments rat renal mineralocorticoid receptor selectivity via 11beta-hydroxysteroid dehydrogenase. (1/271)
Glucocorticoid access to renal corticosteroid receptors is regulated by 11beta-hydroxysteroid dehydrogenases (11beta-HSDs), converting 11beta-hydroxyglucocorticoids into inactive 11-ketones. This mechanism plays a key role in maintaining normal salt-water homeostasis and blood pressure. To study whether renal cortical proximal and distal tubular 11beta-HSDs are modulated, upon shifting the electrolyte status (and may thereby contribute to adjusting the salt-water homeostasis), rats were treated for 14 days with diets with low (0.058 w/w%), normal (0.58%, which is the KCl content of standard European laboratory rat food) or high (5.8%) potassium chloride content. In proximal tubules, dietary KCl had no effect regarding corticosterone 11beta-oxidation in intact cells as well as 11beta-HSD1 and 11beta-HSD2 protein (Western blotting) and mRNA levels (semi-quantitative RT-PCR). In distal tubules, the low KCl diet also had no effect. However, distal tubules of rats fed the high KCl diet showed increased corticosterone 11beta-oxidation rates (1.6-fold, P<0.01) and 11beta-HSD2 protein (4-fold, P<0.01), whereas 11beta-HSD1 protein was decreased (no longer detected, P<0.05). Distal tubular 11beta-HSD mRNA levels were not changed upon dietary treatment. Our results suggest that upon dietary KCl loading distal tubular mineralocorticoid receptor selectivity for aldosterone is increased because of enhanced corticosterone 11beta-oxidation. This may contribute to the fine-tuning of salt-water homeostasis by the kidney. (+info)Full induction of rat myometrial 11beta-hydroxysteroid dehydrogenase type 1 in late pregnancy is dependent on intrauterine occupancy. (2/271)
The 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD-1) enzyme catalyses the conversion of the biologically inert glucocorticoid 11-dehydrocorticosterone to active corticosterone (11-oxoreductase activity) in vivo, and it is dramatically up-regulated in uterine myometrium in the days leading up to parturition. 11beta-HSD-1 is likely to enhance local concentrations of glucocorticoid within the myometrium and thus facilitate uterine contractility, but the stimulus for the increase in myometrial 11beta-HSD-1 is unknown. The objective of the present study was to test whether the induction of myometrial 11beta-HSD-1 is dependent on uterine occupancy or systemic hormonal signals of late pregnancy. This involved use of a unilateral pregnancy (ULP) model in which the gravid and nongravid uterine horns are both exposed to the normal systemic hormonal milieu of pregnancy. Western blot analysis showed that the 11beta-HSD-1 signal was only partially induced in the nongravid horn of ULP rats on Day 22 of pregnancy (term: Day 23). Moreover, artificial distension of this nongravid horn had no effect on myometrial 11beta-HSD-1 immunoreactivity or bioactivity at either Day 16 or Day 22 of pregnancy. Removal of fetuses and placentas on Day 18 reduced myometrial 11beta-HSD-1 bioactivity 4 days later, and this effect was not overcome by artificial maintenance of uterine distension. In contrast, after fetectomy at Day 18 (i.e., removal of the fetus but not placenta), myometrial 11beta-HSD-1 bioactivity was largely maintained on Day 22, indicative of placental support for myometrial 11beta-HSD-1 over this period. In conclusion, our data show that full induction of myometrial 11beta-HSD-1 expression and associated 11-oxoreductase bioactivity late in rat pregnancy is dependent upon intrauterine occupancy. Although the hormonal milieu of late pregnancy appears to stimulate myometrial 11beta-HSD-1 marginally, full induction clearly requires an additional stimulus. Manipulations involving fetectomy and artificial uterine distension indicate that the placenta provides at least part of this stimulus, but uterine stretch does not appear to play a role. (+info)Role of 11beta-hydroxysteroid dehydrogenase in nongenomic aldosterone effects in human arteries. (3/271)
The aim of the present study was to demonstrate rapid effects of aldosterone on the Na(+)-H(+) exchanger in strips of human vascular vessels and to determine whether 11beta-hydroxysteroid dehydrogenase enzyme (11beta-HSD) could play a protective role in this response, such as that described for the classic type I mineralocorticoid receptor (MR). The activity of 11beta-HSD isoforms 1 and 2 were measured in fetal and adult arteries. Both isoforms are present in adult and fetal vessels. However, a significant difference in the proportion of each isoform was found. Isoform 1 activity (in pmol x min(-1) x 100 mg(-1) protein) was 42+/-5 in fetal vessels and 29+/-2 in adult arteries, and isoform 2 activity was 78+/-7 in fetal and 12+/-2 in adult tissue. The nongenomic effect of aldosterone on Na(+)-H(+) exchanger activity was measured in strips of chorionic and radial uterine arteries loaded with the pH-sensitive dye 2',7'-bis(2-carboxyethyl)-5,6-carboxyfluorescein. Recordings of intracellular pH (pH(i)) were made by videofluorescence microscopy. Aldosterone (0.5 nmol/L) rapidly increased pH(i), with a half-maximal effect between 2 and 3 nmol/L in both fetal and adult vessels. Ethylisopropylamiloride, a specific inhibitor of the Na(+)-H(+) exchanger, inhibited this effect. The hormone-mediated increase in pH(i) was unaffected by spironolactone, a classic antagonist of MR, but was completely blocked by RU28318. Cortisol (up to 1 micromol/L) had no effect on pH(i), but when applied in the presence of carbenoxolone, a dramatic increase in Na(+)-H(+) exchanger activity was evident. The increments on pH(i) for each cortisol concentration were similar to those observed for aldosterone. These findings suggest that vascular 11beta-HSD plays an active role in maintaining the specificity of the rapid effects of aldosterone. (+info)Novel nuclear corticosteroid binding in rat small intestinal epithelia. (4/271)
When small intestinal epithelial cells are incubated with [(3)H]corticosterone, nuclear binding is displaced neither by aldosterone nor RU-28362, suggesting that [(3)H]corticosterone is binding to a site distinct from mineralocorticoid receptor and glucocorticoid receptor. Saturation and Scatchard analysis of nuclear [(3)H]corticosterone binding demonstrate a single saturable binding site with a relatively low affinity (49 nM) and high capacity (5 fmol/microg DNA). Competitive binding assays indicate that this site has a unique steroid binding specificity, which distinguishes it from other steroid receptors. Steroid specificity of nuclear binding mirrors inhibition of the low 11beta-dehydrogenase activity, suggesting that binding may be to an 11beta-hydroxysteroid dehydrogenase (11betaHSD) isoform, although 11betaHSD1 is not present in small intestinal epithelia and 11betaHSD2 does not colocalize intracellularly with the binding site. In summary, a nuclear [(3)H]corticosterone binding site is present in small intestinal epithelia that is distinct from other steroid receptors and shares steroid specificity characteristics with 11betaHSD2 but is distinguishable from the latter by its distinct intracellular localization. (+info)Peroxisome proliferator-activated receptor-gamma ligands inhibit adipocyte 11beta -hydroxysteroid dehydrogenase type 1 expression and activity. (5/271)
Peroxisome proliferator-activated receptor-gamma (PPARgamma) has been shown to play an important role in the regulation of expression of a subclass of adipocyte genes and to serve as the molecular target of the thiazolidinedione (TZD) and certain non-TZD antidiabetic agents. Hypercorticosteroidism leads to insulin resistance, a variety of metabolic dysfunctions typically seen in diabetes, and hypertrophy of visceral adipose tissue. In adipocytes, the enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD-1) converts inactive cortisone into the active glucocorticoid cortisol and thereby plays an important role in regulating the actions of corticosteroids in adipose tissue. Here, we show that both TZD and non-TZD PPARgamma agonists markedly reduced 11beta-HSD-1 gene expression in 3T3-L1 adipocytes. This diminution correlated with a significant decrease in the ability of the adipocytes to convert cortisone to cortisol. The half-maximal inhibition of 11beta-HSD-1 mRNA expression by the TZD, rosiglitazone, occurred at a concentration that was similar to its K(d) for binding PPARgamma and EC(50) for inducing adipocyte differentiation thereby indicating that this action was PPARgamma-dependent. The time required for the inhibitory action of the TZD was markedly greater for 11beta-HSD-1 gene expression than for leptin, suggesting that these genes may be down-regulated by different molecular mechanisms. Furthermore, whereas regulation of PPARgamma-inducible genes such as phosphoenolpyruvate carboxykinase was maintained when cellular protein synthesis was abrogated, PPARgamma agonist inhibition of 11beta-HSD-1 and leptin gene expression was ablated, thereby supporting the conclusion that PPARgamma affects the down-regulation of 11beta-HSD-1 indirectly. Finally, treatment of diabetic db/db mice with rosiglitazone inhibited expression of 11beta-HSD-1 in adipose tissue. This decrease in enzyme expression correlated with a significant decline in plasma corticosterone levels. In sum, these data indicate that some of the beneficial effects of PPARgamma antidiabetic agents may result, at least in part, from the down-regulation of 11beta-HSD-1 expression in adipose tissue. (+info)Functional expression, characterization, and purification of the catalytic domain of human 11-beta -hydroxysteroid dehydrogenase type 1. (6/271)
11-beta-hydroxysteroid dehydrogenase type 1 catalyzes the conversion of cortisone to hormonally active cortisol and has been implicated in the pathogenesis of a number of disorders including insulin resistance and obesity. The enzyme is a glycosylated membrane-bound protein that has proved difficult to purify in an active state. Extracted enzyme typically loses the reductase properties seen in intact cells and shows principally dehydrogenase activity. The C-terminal catalytic domain is known to contain a disulfide bond and is located within the lumen of the endoplasmic reticulum, anchored to the membrane by a single N-terminal transmembrane domain. We report here the functional expression of the catalytic domain of the human enzyme, without the transmembrane domain and the extreme N terminus, in Escherichia coli. Moderate levels of soluble active protein were obtained using an N-terminal fusion with thioredoxin and a 6xHis tag. In contrast, the inclusion of a 6xHis tag at the C terminus adversely affected protein solubility and activity. However, the highest levels of active protein were obtained using a construct expressing the untagged catalytic domain. Nonreducing electrophoresis revealed the presence of both monomeric and dimeric disulfide bonded forms; however, mutation of a nonconserved cysteine residue resulted in a recombinant protein with no intermolecular disulfide bonds but full enzymatic activity. Using the optimal combination of plasmid construct and E. coli host strain, the recombinant protein was purified to apparent homogeneity by single step affinity chromatography. The purified protein possessed both dehydrogenase and reductase activities with a K(m) of 1.4 micrometer for cortisol and 9.5 micrometer for cortisone. This study indicates that glycosylation, the N-terminal region including the transmembrane helix, and intermolecular disulfide bonds are not essential for enzyme activity and that expression in bacteria can provide active recombinant protein for future structural and functional studies. (+info)A transgenic model of visceral obesity and the metabolic syndrome. (7/271)
The adverse metabolic consequences of obesity are best predicted by the quantity of visceral fat. Excess glucocorticoids produce visceral obesity and diabetes, but circulating glucocorticoid levels are normal in typical obesity. Glucocorticoids can be produced locally from inactive 11-keto forms through the enzyme 11beta hydroxysteroid dehydrogenase type 1 (11beta HSD-1). We created transgenic mice overexpressing 11beta HSD-1 selectively in adipose tissue to an extent similar to that found in adipose tissue from obese humans. These mice had increased adipose levels of corticosterone and developed visceral obesity that was exaggerated by a high-fat diet. The mice also exhibited pronounced insulin-resistant diabetes, hyperlipidemia, and, surprisingly, hyperphagia despite hyperleptinemia. Increased adipocyte 11beta HSD-1 activity may be a common molecular etiology for visceral obesity and the metabolic syndrome. (+info)Correlation between decrease of 11beta-hydroxysteroid dehydrogenase activity and hypokalemia induced by furosemide in rats. (8/271)
AIM: To investigate the correlation between decrease of 11beta-hydroxysteroid dehydrogenase (11beta-HSD) activity and hypokalemia induced by furosemide (Fur) in rats. METHODS: SD rats were given single dose or successive doses of Fur by gavage. The activity of 11beta-HSD was evaluated by measuring the ratio of 11-dehydrocorticosterone (A) and corticosterone (B) in urine and conversion rate of B to A in renal cortex microsome preparation was determined with HPLC. RESULTS: After giving single dose of Fur (40, 100, and 250 mg/kg) or multiple doses of Fur (10, 20, and 100 mg/kg, bid x 20 d), the ratio of A/B was reduced by 29.0 %, 58.6 %, and 60.9 % at 0 - 2 h; 14.4 %, 36.0 %, and 44.9 %, respectively; the conversion rate of B to A was decreased by 29 %, 33 %, and 37 %; 6 %, 17 %, and 23 %, respectively. The serum potassium was significantly reduced by multiple doses of Fur (20 and 100 mg/kg, bid x 20 d) (P < 0.01). The reduction in serum potassium was positively correlated with the lowering of A/B ratio and the conversion of B to A (P < 0.01). CONCLUSION: The inhibition of renal 11beta-HSD activity may be another new biochemical mechanism for hypokalemia induced by Fur. (+info)"11beta-hydroxysteroid dehydrogenase type 1: a tissue-specific regulator of glucocorticoid response". Endocrine Reviews. 25 (5 ... 5-beta THF), reactions for which 5-alpha reductase and 5-beta reductase are the rate-limiting factors, respectively. 5-Beta ... The cells do not lose all their fight-or-flight override because of interleukin-1's synergism with CRH. Cortisol even has a ... "Cortisol release from adipose tissue by 11beta-hydroxysteroid dehydrogenase type 1 in humans". Diabetes. 58 (1): 46-53. doi: ...
... beta}-hydroxysteroid dehydrogenase type 1 activity". Endocrinology. 146 (6): 2539-43. doi:10.1210/en.2005-0117. PMID 15774558. ... "Mutations in the genes encoding 11beta-hydroxysteroid dehydrogenase type 1 and hexose-6-phosphate dehydrogenase interact to ... "Mutations in the genes encoding 11beta-hydroxysteroid dehydrogenase type 1 and hexose-6-phosphate dehydrogenase interact to ... "Cortisone-reductase deficiency associated with heterozygous mutations in 11beta-hydroxysteroid dehydrogenase type 1". ...
... possible interference with type 1 11beta-hydroxysteroid dehydrogenase-mediated processes". J. Steroid Biochem. Mol. Biol. 104 ( ... "CYP7B generates a selective estrogen receptor beta agonist in human prostate". J. Clin. Endocrinol. Metab. 89 (6): 2928-35. doi ... 316 (1): 158-64. doi:10.1016/j.bbrc.2004.02.029. PMID 15003524. Yau JL, Rasmuson S, Andrew R, Graham M, Noble J, Olsson T, ... "Entrez Gene: CYP7B1 cytochrome P450, family 7, subfamily B, polypeptide 1". Stapleton G, Steel M, Richardson M, Mason JO, Rose ...
11beta-hydroxysteroid dehydrogenase type 1- a tissue-specific amplifier of glucocorticoid action". Endocrinology. 142 (4): 1371 ... Seckl JR (January 1997). "11beta-Hydroxysteroid dehydrogenase in the brain: a novel regulator of glucocorticoid action?". Front ... The systematic name of this enzyme class is 11beta-hydroxysteroid:NADP+ 11-oxidoreductase. Other names in common use include ... the two substrates of this enzyme are 11beta-hydroxysteroid and NADP+, whereas its 3 products are 11-oxosteroid, NADPH, and H+ ...
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... beta-hydroxysteroid dehydrogenase isoforms using reverse-transcriptase-polymerase chain reaction and localization of the type 2 ... Wake DJ, Walker BR (February 2006). "Inhibition of 11beta-hydroxysteroid dehydrogenase type 1 in obesity". Endocrine. 29 (1): ... Agarwal AK (November 2003). "Cortisol metabolism and visceral obesity: role of 11beta-hydroxysteroid dehydrogenase type I ... "11beta-Hydroxysteroid dehydrogenase types 1 and 2 are up- and downregulated in cortisol-secreting adrenal adenomas". Journal of ...
3-hydroxysteroid dehydrogenases MeSH D08.811.682.047.436.350.100 --- 3alpha-hydroxysteroid dehydrogenase (B-specific) MeSH ... myosin type iii MeSH D08.811.277.040.025.525.843 --- myosin type iv MeSH D08.811.277.040.025.525.875 --- myosin type v MeSH ... dopamine beta-hydroxylase MeSH D08.811.682.690.708.392 --- fatty acid desaturases MeSH D08.811.682.690.708.392.312 --- beta- ... 20-hydroxysteroid dehydrogenases MeSH D08.811.682.047.436.400.074 --- 20alpha-hydroxysteroid dehydrogenase MeSH D08.811.682.047 ...
2003). "Mutations in the genes encoding 11beta-hydroxysteroid dehydrogenase type 1 and hexose-6-phosphate dehydrogenase ... Ikegwuonu FI, Jefcoate CR (1999). "Evidence for the involvement of the fatty acid and peroxisomal beta-oxidation pathways in ... Beutler E, Morrison M (1968). "Localization and characteristics of hexose 6-phosphate dehydrogenase (glucose dehydrogenase)". J ... "An autosomal glucose-6-phosphate dehydrogenase (hexose-6-phosphate dehydrogenase) polymorphism in human saliva". Hum. Hered. 26 ...
"17 beta-hydroxysteroid dehydrogenase type XI localizes to human steroidogenic cells". Endocrinology. 144 (5): 2084-91. doi: ... "Entrez Gene: HSD17B11 hydroxysteroid (17-beta) dehydrogenase 11". Li KX, Smith RE, Krozowski ZS (1999). "Cloning and expression ... Estradiol 17-beta-dehydrogenase 11 is an enzyme that in humans is encoded by the HSD17B11 gene. GRCh38: Ensembl release 89: ... Haeseleer F, Palczewski K (2000). "Short-chain dehydrogenases/reductases in retina". Methods in Enzymology. 316: 372-83. doi: ...
... the type II 3 beta-hydroxysteroid dehydrogenase gene in a patient with classic salt-wasting 3 beta-hydroxysteroid dehydrogenase ... of type II 3 beta-hydroxysteroid dehydrogenase gene in Japanese patients with classical 3 beta-hydroxysteroid dehydrogenase ... 1992). "Structure of the human type II 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase (3 beta-HSD) gene: adrenal ... 1995). "A novel missense mutation in the type II 3 beta-hydroxysteroid dehydrogenase gene in a family with classical salt- ...
Moghrabi N, Head JR, Andersson S (Nov 1997). "Cell type-specific expression of 17 beta-hydroxysteroid dehydrogenase type 2 in ... Oliveira IO, Lhullier C, Brum IS, Spritzer PM (Sep 2003). "Gene expression of type 2 17 beta hydroxysteroid dehydrogenase in ... 17β-Hydroxysteroid dehydrogenase 2 (17β-HSD2) is an enzyme of the 17β-hydroxysteroid dehydrogenase (17β-HSD) family that in ... "The human type II 17 beta-hydroxysteroid dehydrogenase gene encodes two alternatively spliced mRNA species". DNA and Cell ...
42 (1): 1-23. doi:10.1016/j.jchemneu.2011.05.003. PMC 3148274 . PMID 21605659. Dong, HW; Petrovich, GD; Watts, AG; Swanson, LW ... 1115 (1): 54-64. doi:10.1016/j.brainres.2006.07.091. PMID 16935272. Geerling, JC; Kawata, M; Loewy, AD (Jan 20, 2006). " ... Geerling, JC; Engeland, WC; Kawata, M; Loewy, AD (Jan 11, 2006). "Aldosterone target neurons in the nucleus tractus solitarius ... Geerling, JC; Loewy, AD (Aug 1, 2006). "Aldosterone-sensitive neurons in the nucleus of the solitary tract: bidirectional ...
3(or 17)beta-hydroxysteroid dehydrogenase at the US National Library of Medicine Medical Subject Headings (MeSH) Molecular and ... Soubhye J, Alard IC, van Antwerpen P, Dufrasne F (2015). "Type 2 17-β hydroxysteroid dehydrogenase as a novel target for the ... Yang SY, He XY, Isaacs C, Dobkin C, Miller D, Philipp M (2014). "Roles of 17β-hydroxysteroid dehydrogenase type 10 in ... Aka JA, Mazumdar M, Chen CQ, Poirier D, Lin SX (April 2010). "17beta-hydroxysteroid dehydrogenase type 1 stimulates breast ...
... type 2 deficiency 17 alpha hydroxylase deficiency 17 beta hydroxysteroide dehydrogenase deficiency 17-beta-hydroxysteroid ... type 3, rare (NIH) 3 beta hydroxysteroid dehydrogenase deficiency 3 hydroxyisobutyric aciduria 3 methylcrotonic aciduria 3 ... Diseases Alphabetical list 0-9 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z See also Health Exercise Nutrition 11 beta ... dehydrogenase deficiency, rare (NIH) 17q21.31 microdeletion syndrome 18-Hydroxylase deficiency, rare (NIH) 18p deletion ...
... estradiols having inhibitory effect on human placental estradiol 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD type 1)". ... "Entrez Gene: HSD17B1 Hydroxysteroid (17-beta) dehydrogenase 1". Saloniemi T, Jokela H, Strauss L, Pakarinen P, Poutanen M (2012 ... Aka JA, Mazumdar M, Chen CQ, Poirier D, Lin SX (Apr 2010). "17beta-hydroxysteroid dehydrogenase type 1 stimulates breast cancer ... Sawetawan C, Milewich L, Word RA, Carr BR, Rainey WE (Mar 1994). "Compartmentalization of type I 17 beta-hydroxysteroid ...
This type of receptor becomes activated upon ligand binding. After a hormone binds to the corresponding receptor, the newly ... 1 (1). doi:10.15347/wjm/2014.005. ISSN 2002-4436. Omar, HR; Komarova, I; El-Ghonemi, M; Fathy, A; Rashad, R; Abdelmalak, HD; ... This enzyme, 11-beta hydroxysteroid dehydrogenase type II (Protein:HSD11B2), catalyzes the deactivation of glucocorticoids to ... 11 ed)., Saunders Elsevier, Philadelphia, pp. 445-504. Bennett PN and Brown MJ (2008) "Adrenal corticosteroids, antagonists, ...
Studies on the stably transfected isoforms and localization of the type 2 isozyme within renal tissue". Steroids. 62 (1): 77-82 ... 11α-OHP is a more potent inhibitor of 11β-HSD than enoxolone (glycyrrhetinic acid) or carbenoxolone in vitro (IC50 = 0.9 nM; ... 11 alpha-Hydroxyprogesterone (11 alpha OH-P) was an order of magnitude more potent a competitive inhibitor of the 11 beta HSD-2 ... In 1995, 11α-OHP, along with its epimer 11β-hydroxyprogesterone, was identified as a very potent competitive inhibitor of both ...
Licorice inhibits the 11-beta hydroxysteroid dehydrogenase type II (Protein:HSD11B2) enzyme resulting in inappropriate ...
Mindnich R, Möller G, Adamski J (2004). "The role of 17 beta-hydroxysteroid dehydrogenases". Mol. Cell. Endocrinol. 218 (1-2): ... Soubhye J, Alard IC, van Antwerpen P, Dufrasne F (2015). "Type 2 17-β hydroxysteroid dehydrogenase as a novel target for the ... 3(or+17)beta-hydroxysteroid+dehydrogenase at the US National Library of Medicine Medical Subject Headings (MeSH) ... Talalay P, Dobson MM (December 1953). "Purification and properties of a beta-hydroxysteroid dehydrogenase". The Journal of ...
Rheault P, Dufort I, Soucy P, Luu-The V (1999). "Assignment of HSD17B5 encoding type 5 17 beta-hydroxysteroid dehydrogenase to ... 11beta-PGF2 to PGD2. It may play an important role in the pathogenesis of allergic diseases such as asthma, and may also have a ... 3-alpha hydroxysteroid dehydrogenase, type II)". Tian Y, Zhao L, Zhang H, Liu X, Zhao L, Zhao X, Li Y, Li J (2014). "AKR1C3 ... also known as 17β-hydroxysteroid dehydrogenase type 5 (17β-HSD5, HSD17B5) is a key steroidogenic enzyme that in humans is ...
"Abundant type 10 17 beta-hydroxysteroid dehydrogenase in the hippocampus of mouse Alzheimer's disease model". Brain Research. ... 17-β-Hydroxysteroid dehydrogenase X (HSD10) also known as 3-hydroxyacyl-CoA dehydrogenase type-2 is a mitochondrial enzyme that ... 17-beta) dehydrogenase 10". He XY, Yang YZ, Schulz H, Yang SY (Jan 2000). "Intrinsic alcohol dehydrogenase and hydroxysteroid ... Yang SY, He XY, Isaacs C, Dobkin C, Miller D, Philipp M (Sep 2014). "Roles of 17β-hydroxysteroid dehydrogenase type 10 in ...
Dehydrogenase/reductase (SDR family) member 7B is an enzyme encoded by the DHRS7B gene in humans, found on chromosome 17p11.2. ... CD44 is an antigen found on the surface of most cell types and functions as a receptor that binds tissue macromolecules. ... DHRS7B is a member of the short chain dehydrogenase/reductase (SDR) superfamily and possesses characteristic features of an SDR ... Dehydrogenase/reductase (SDR family) member 7B". "Genecards: DHRS7B Gene protein-coding GIFtS 47". Tannin GM, Agarwal AK, ...
These hormones and medications include insulin, epinephrine, and other beta agonists (e.g. salbutamol or salmeterol), and ... Type B intercalated cells in the collecting duct reabsorb H+ and secrete HCO3. Protons are reabsorbed via both H+-K+ATPases and ... this facilitated diffusion occurs in both Type B intercalated cells and Principal cells in the collecting duct). 2) Metabolic ... Hypertension and hypokalemia can also be seen with a deficiency of the 11-beta-hydroxysteroid dehydrogenase type 2 enzyme which ...
17 beta-dihydroxy-17-methyl-1, 4-androstadien-3-one and related compounds". Steroids. 43 (3): 271-82. doi:10.1016/0039-128x(84) ... 27 (3 Pt 1): 421-5. doi:10.1161/01.hyp.27.3.421. PMID 8698448. Fürstenberger C, Vuorinen A, Da Cunha T, Kratschmar DV, Saugy M ... In accordance, 11α- and 11β-hydroxyprogesterone are known to be potent inhibitors of 11β-hydroxysteroid dehydrogenase (11β-HSD ... ISBN 978-1-4757-2085-3. Felippone F, Resnati G, Scolastico C, Tronconi G (1984). "Synthesis of 2-carboxy-11 beta, ...
"Human placental 17 beta-estradiol dehydrogenase and 20 alpha-hydroxysteroid dehydrogenase. Two activities at a single enzyme ... Akinola LA, Poutanen M, Vihko R, Vihko P (July 1997). "Expression of 17beta-hydroxysteroid dehydrogenase type 1 and type 2, ... Other names in common use include 20alpha-hydroxy steroid dehydrogenase, 20alpha-hydroxy steroid dehydrogenase, 20alpha-HSD, ... hydroxysteroid dehydrogenase AKR1C1 Shikita M, Inano H, Tamaoki B (1967). "Further studies on 20-alpha-hydroxysteroid ...
17β-hydroxysteroid dehydrogenase deficiency. *aromatase excess syndrome. *Androgen receptor (Androgen insensitivity syndrome) ... a type 2 diabetic will have lost about half of their beta cells.[52] Fatty acids in the beta cells activate FOXO1, resulting in ... Xi B, Li S, Liu Z, Tian H, Yin X, Huai P, Tang W, Zhou D, Steffen LM (2014). "Intake of fruit juice and incidence of type 2 ... Type 2 diabetes is due to insufficient insulin production from beta cells in the setting of insulin resistance.[13] Insulin ...
11Beta-hydroxysteroid dehydrogenase type 1 in human disease: a novel therapeutic target.. Tomlinson JW1. ... At a tissue specific level, the enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) locally regenerates active ... Publication type, MeSH terms, Substances. Publication type. *Review. MeSH terms. *11-beta-Hydroxysteroid Dehydrogenase Type 1/ ... Here we review the role of 11beta-HSD1 in human disease and discuss the impact of selective 11beta-HSD1 inhibition. ...
Human 11beta-Hydroxysteroid Dehydrogenase Type 1 in complex with AZD8329. *DOI: 10.2210/pdb4P38/pdb ... Corticosteroid 11-beta-dehydrogenase isozyme 1. A, B. 265. Homo sapiens. Mutation(s): 0 Gene Names: HSD11B1, HSD11, HSD11L, ... 4-[4-(2-adamantylcarbamoyl)-5-tert-butyl-pyrazol-1-yl]benzoic acid. C25 H31 N3 O3. XWBXJBSVYVJAMZ-RCQAVAAASA-N. Ligand ... Inhibition of 11β-HSD1 is viewed as a potential target for the treatment of obesity and other elements of the metabolic ...
Resource Type:. Journal Article. Resource Relation:. Journal Name: Acta Crystallogr. F; Journal Volume: 68; Journal Issue: (5 ... Qin, Wenying ; Judge, Russell A. ; Longenecker, Kenton L. ; Solomon, Larry R. ; Harlan, John E. [1] + Show Author Affiliations ... beta]-hydroxysteroid dehydrogenase type 1 ... a case study with human 11[beta]-hydroxysteroid dehydrogenase ... Title: On-column ligand exchange for structure-based drug design: a case study with human 11[ ...
... is developing 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitors for the ... Research Type 2 diabetes mellitus Most Recent Events * 21 Oct 2016 11-beta hydroxysteroid dehydrogenase type 1 inhibitors are ... 16 Jul 2016 No recent reports of development identified for research development in Type-2-diabetes-mellitus in France ... 28 May 2009 Early research in Type-2 diabetes mellitus in France (unspecified route) ...
... ... 11beta-hydroxysteroid dehydrogenase type 1 regulates glucocorticoid-induced insulin resistance in skeletal muscle. 2009, 58 (11 ... 11beta-Hydroxysteroid dehydrogenase type 1 regulates insulin and glucagon secretion in pancreatic islets. ... Within skeletal muscle, 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) converts cortisone (11-dehydrocorticosterone ...
Within skeletal muscle, 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) converts cortisone (11-dehydrocorticosterone ... A1 (selective 11beta-HSD1 inhibitor) abolished enzyme activity and blocked the increase in pSer(307) IRS1 and reduction in ... Selective 11beta-HSD1 inhibition decreases pSer(307) IRS1, increases pThr(308) Akt/PKB, and decreases lipogenic and lipolytic ... In C57Bl6/J mice, the selective 11beta-HSD1 inhibitor, A2, decreased fasting blood glucose levels and improved insulin ...
11-Beta-Hydroxysteroid Dehydrogenase Type 1 (Hsd11b1) Antibody 由Abbexa供应,该产品简介:11-Beta-Hydroxysteroid Dehydrogenase Type 1 ( ... 注:1.可以使用快捷键Alt+S或Ctrl+Enter发送信息!. 2.如有必要,请您留下您的详细联系方式! ... 产品名称:11-Beta-Hydroxysteroid Dehydrogenase Type 1 (Hsd11b1) Antibody ... 地址:上海市闵
Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes. Diabetes 2003;52:102-110pmid:12502499. ... 11Beta-hydroxysteroid dehydrogenase type 1 and obesity. Front Horm Res 2008;36:146-164pmid:18230901. ... 11Beta-hydroxysteroid dehydrogenase type 1 regulates insulin and glucagon secretion in pancreatic islets. Diabetologia 2008;51: ... Preadipocyte 11beta-hydroxysteroid dehydrogenase type 1 is a keto-reductase and contributes to diet-induced visceral obesity in ...
Incubation of beta-cells in the presence of 11-dehydrocorticosterone leads to a dose-dependent inhibition of insulin release, ... carried out by 11beta-hydroxysteroid dehydrogenases (11beta-HSDs). In this study, we determined the role of glucocorticoid ... Inhibition of 11beta-HSD activity by carbenoxolone reverses inhibition of insulin release. The presence of 11beta-HSD in islets ... Expression of type 1 11beta-HSD mRNA was detected by reverse transcriptase-polymerase chain reaction in islets isolated from ob ...
Reduced adipose 11beta-HSD1 expression and increased plasma cortisol during longer therapy with rosiglitazone probably reflect ... In 12 healthy men, 4-5 wk of rosiglitazone increased insulin sensitivity during insulin infusion but did not change 11beta-HSD1 ... OBJECTIVE: Our objective was to test whether PPAR agonists alter cortisol secretion and peripheral regeneration by 11beta-HSD1 ... In 12 men with type 2 diabetes 12 wk of rosiglitazone reduced arteriovenous cortisone extraction across abdominal sc adipose ...
The latter effect is accomplished by two different 11beta-hydroxysteroid dehydrogenase isozymes, constituting a shuttle system ... The type 2 enzyme is an exclusive NAD+ dependent dehydrogenase of glucocorticoids, thus protecting the mineralocorticoid ... Whereas the type 1 enzyme (11beta-HSD1) is in vitro a NADP(H)- dependent bidirectional enzyme, it reduces in most instances in ... Importantly, 11beta-HSD1 activity appears to be intrinsically linked to all features of the metabolic syndrome, which could at ...
Heterologous production of 11beta-HSD1, devoid of its N-terminal transmembrane segment, is possible but yields only small ... Here we show that the soluble portion of recombinant 11beta-HSD1 produced in E. coli is found mainly as multimeric aggregates ... Moreover, active site titration of human 11beta-HSD1 revealed that at least 75% of the protein in a typical preparation ... By co-overexpressing GroEL/ES and adding an 11beta-HSD1 inhibitor during protein synthesis, we have increased the accumulation ...
... beta-hydroxysteroid dehydrogenase isoforms using reverse-transcriptase-polymerase chain reaction and localization of the type 2 ... Wake DJ, Walker BR (February 2006). "Inhibition of 11beta-hydroxysteroid dehydrogenase type 1 in obesity". Endocrine. 29 (1): ... Agarwal AK (November 2003). "Cortisol metabolism and visceral obesity: role of 11beta-hydroxysteroid dehydrogenase type I ... "11beta-Hydroxysteroid dehydrogenase types 1 and 2 are up- and downregulated in cortisol-secreting adrenal adenomas". Journal of ...
Regulation of glucocorticoid receptor alpha and beta isoforms and type I 11beta-hydroxysteroid dehydrogenase expression in ... 11Beta-hydroxysteroid dehydrogenase type 1: a tissue-specific regulator of glucocorticoid response. Endocr Rev 2004;25:831-866 ... 11beta-hydroxysteroid dehydrogenase type 1 activity in lean and obese males with type 2 diabetes mellitus. J Clin Endocrinol ... Type 2 diabetes and metabolic syndrome are associated with increased expression of 11beta-hydroxysteroid dehydrogenase 1 in ...
11beta-HSD1) have considerable potential as treatments for metabolic diseases, such as diabetes mellitus type 2 or obesity. ... inhibition for 11beta-HSD1 at 10 microM and exhibited IC50 values in the low micromolar range. The preliminary SAR study ... the discovery and synthesis of a series of novel benzothiazole derivatives and their inhibitory activities against 11beta-HSD1 ... Docking studies with the benzothiazole derivative 1 into the crystal structure of human 11beta-HSD1 revealed how the molecule ...
Their findings showed that the D-bifunctional protein plays an essential role in the peroxisomal beta-oxidation pathway that ... Biochemical analysis showed that the 3-hydroxyacyl-CoA dehydrogenase activity of the D-bifunctional protein was completely ... 11 beta hydroxysteroid dehydrogenase and the syndrome of apparent mineralocorticoid excess. Media:. ... 11 beta hydroxysteroid dehydrogenase and the syndrome of apparent mineralocorticoid excess. In 2 unrelated patients, Ulick et ...
11beta-hydroxysteroid dehydrogenase type 1- a tissue-specific amplifier of glucocorticoid action". Endocrinology. 142 (4): 1371 ... Seckl JR (January 1997). "11beta-Hydroxysteroid dehydrogenase in the brain: a novel regulator of glucocorticoid action?". Front ... The systematic name of this enzyme class is 11beta-hydroxysteroid:NADP+ 11-oxidoreductase. Other names in common use include ... the two substrates of this enzyme are 11beta-hydroxysteroid and NADP+, whereas its 3 products are 11-oxosteroid, NADPH, and H+ ...
Rat 11-Beta-Hydroxysteroid Dehydrogenase Type 1 (HSD11B1) ELISA Kit Abbexa Ltd ...
11beta-HSD1 have dual enzyme activities like the recently described 7alpha-hydroxysteroid dehydrogenase/11beta-hydroxysteroid ... 11beta-HSD1) catalyzes the conversion of cortisone to its active receptor-binding derivative cortisol, whereas 11beta-HSD type ... We report here on the in vitro oxysterol-metabolizing properties of human and rodent 11beta-HSD1. The enzyme, either as full- ... Specific inhibitors against the type 1 enzyme lower intracellular levels of glucocorticoid hormone, with an important clinical ...
Association studies between the HSD11B2 gene (encoding human 11beta-hydroxysteroid dehydrogenase type 2), type 1 diabetes ... Mutations in the HSD11B2 gene (encoding human 11beta-hydroxysteroid dehydrogenase type 2) explain the syndrome of apparent ... frequency of HSD11B2 short alleles in the diabetic groups may reflect reduced renal 11beta-hydroxysteroid dehydrogenase type 2 ... Publication type, MeSH terms, Substances. Publication type. *Research Support, Non-U.S. Govt ...
Genetic variation in 11beta-hydroxysteroid dehydrogenase type 1 predicts adrenal hyperandrogenism among lean women with ... impaired regeneration of active cortisol from inert cortisone by 11beta-hydroxysteroid dehydrogenase (11beta-HSD1) results in ... Publication type, MeSH terms, Substances. Publication type. *Research Support, Non-U.S. Govt ... 11beta-HSD1 deficiency may protect against obesity and its metabolic consequences because of impaired regeneration of cortisol ...
Elevenbeta-hydroxysteroid dehydrogenase type 1 (11beta-HSD-1), a key intracellular enzyme which catalyses the conversion of ... If confirmed, these results would prompt the development of selective and tissue-specific 11beta-HSD-1 inhibitors to decrease ... 11β-hydroxysteroid dehydrogenase type 1; Cortisol; Cortisone; Metabolic syndrome. Settore Scientifico Disciplinare: Settore MED ... are less convincing with several case control and cross-sectional studies showing an association between with 11beta-HSD-1 ...
Altered endogenous glucocorticoid metabolism, including 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), which ... Two women and five men were diagnosed with type 2 diabetes. In women, adipose 11beta-HSD1 expression was increased in patients ... Increased adipose 11beta-HSD1 expression in women may contribute to glucose intolerance. Enhanced 5alphaR activity in both ... Altered endogenous glucocorticoid metabolism, including 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), which ...
Publication types * Research Support, Non-U.S. Govt MeSH terms * 11-beta-Hydroxysteroid Dehydrogenase Type 1 / metabolism ... Trevor Teich 1 , Jacklyn A Pivovarov 1 , Deanna P Porras 1 , Emily C Dunford 1 , Michael C Riddell 1 ... 1 Muscle Health Research Centre, School of Kinesiology and Health Science, York University , Toronto, Ontario , Canada. ... and two detrained groups which had their wheels locked and were reintroduced to ad libitum feeding for 1 wk. The wheel locked ...
11beta-hydroxysteroid dehydrogenase type 1 regulates glucocorticoid-induced insulin resistance in skeletal muscle. ... Characterization of the human, mouse and rat PGC1 beta (peroxisome-proliferator-activated receptor-gamma co-activator 1 beta) ... 11.. The use of spherical reconstituted high density lipoprotein for the measurement of cholesteryl ester transfer protein ... Lipid derivatives activate GPR119 and trigger GLP-1 secretion in primary murine L-cells. ...
Hsd11b1GlucocorticoidsHumansGeneIsozymeCorticosteroidEnzyme 11InhibitionInhibitors of humanHexose-6-phosphate dehydrogenaseRodentsMice2016ReductaseActive cortisolHSD11B2VivoRenalGenesObeseCortisol by 11RegulationProtein-coupled receptorSubcutaneous adipose tissueSelective 11HumanAssociated with insulin resistanceIsletsDiabetes mellitusIsozymesCompoundsPatients with type 2 diabetPlacentalConversion of cortisoneTissue specificCONCLUSIONSAldosteroneMetabolic syndromeActivityTherapeuticCardiovascularHepaticMRNA2018Intracellular
- Your search returned 1 HSD11B1 ELISA ELISA Kit across 1 supplier. (biocompare.com)
- The enzyme 11-beta hydroxysteroid dehydrogenase type 1 (HSD11B1) converts inactive cortisone to active cortisol in a process mediated by the enzyme hexose-6-phosphate dehydrogenase (H6PD). (medworm.com)
- Corticosteroid 11 Beta Dehydrogenase Isozyme 1 (11 Beta Hydroxysteroid Dehydrogenase 1 or Short Chain Dehydrogenase/Reductase Family 26C Member 1 or HSD11B1 or EC 1.1.1.146) - 11beta-hydroxysteroid dehydrogenase type 1 is an NADPH-dependent enzyme highly expressed in key metabolic tissues including liver, adipose tissue, and the central nervous system. (marketresearch.com)
- Corticosteroid 11 Beta Dehydrogenase Isozyme 1 (11 Beta Hydroxysteroid Dehydrogenase 1 or Short Chain Dehydrogenase/Reductase Family 26C Member 1 or HSD11B1 or EC 1.1.1.146) pipeline Target constitutes close to 13 molecules. (marketresearch.com)
- The latest report Corticosteroid 11 Beta Dehydrogenase Isozyme 1 - Pipeline Review, H2 2018, outlays comprehensive information on the Corticosteroid 11 Beta Dehydrogenase Isozyme 1 (11 Beta Hydroxysteroid Dehydrogenase 1 or Short Chain Dehydrogenase/Reductase Family 26C Member 1 or HSD11B1 or EC 1.1.1.146) targeted therapeutics, complete with analysis by indications, stage of development, mechanism of action (MoA), route of administration (RoA) and molecule type. (marketresearch.com)
- It also reviews key players involved in Corticosteroid 11 Beta Dehydrogenase Isozyme 1 (11 Beta Hydroxysteroid Dehydrogenase 1 or Short Chain Dehydrogenase/Reductase Family 26C Member 1 or HSD11B1 or EC 1.1.1.146) targeted therapeutics development with respective active and dormant or discontinued projects. (marketresearch.com)
- Regulation of lipid metabolism by glucocorticoids and 11β-HSD1 in skeletal muscle. (lenus.ie)
- Glucocorticoids and 11β-HSD1 are major regulators of intramyocellular protein metabolism. (lenus.ie)
- RESEARCH DESIGN AND METHODS: Rodent and human cell cultures, whole-tissue explants, and animal models were used to determine the impact of glucocorticoids and selective 11beta-HSD1 inhibition upon insulin signaling and action. (ox.ac.uk)
- Abnormally elevated intracellular regeneration of glucocorticoids by the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in fat or liver may underlie pathophysiological aspects of the metabolic syndrome. (diabetesjournals.org)
- 11β-HSD1 is elevated in islets of diabetic rodents ( 4 - 6 ), where it was hypothesized to promote β-cell failure by amplifying the suppressive effects of glucocorticoids on insulin secretion ( 7 , 8 ). (diabetesjournals.org)
- Their effects primarily depend on their binding to intracellular receptors leading to altered target gene transcription as well as on cell-type specific biotransformation between 11beta-hydroxy glucocorticoids and their 11-oxo metabolites. (ox.ac.uk)
- The type 2 enzyme is an exclusive NAD+ dependent dehydrogenase of glucocorticoids, thus "protecting" the mineralocorticoid receptor against illicit occupation by cortisol. (ox.ac.uk)
- Animal studies and pharmacological experiments suggest further unrelated target areas, for example improvement of cognitive function and treatment of glaucoma, due to the role of glucocorticoids and cellular activation by 11beta-HSD1 in these pathologies. (ox.ac.uk)
- Excess glucocorticoids , a type of steroid that may be administered as a drug. (healthengine.com.au)
- Sakamuri VP, Ananthathmakula P, Veettil GN, Ayyalasomayajula V (2011) Vitamin A decreases pre-receptor amplification of glucocorticoids in obesity-study on the effect of Vitamin A on 11 beta-hydroxysteroid dehydrogenase type 1 activity in liver and visceral fat of WNIN/Ob obese rats. (springer.com)
- OBJECTIVE: Our objective was to test whether PPAR agonists alter cortisol secretion and peripheral regeneration by 11beta-HSD1 in humans and whether reduced cortisol action contributes to metabolic effects of PPARgamma agonists. (ox.ac.uk)
- CONCLUSIONS: Neither PPARalpha nor PPARgamma agonists down-regulate 11beta-HSD1 or cortisol secretion acutely in humans. (ox.ac.uk)
- In humans, 11β-HSD1 also may be important to metabolic health, and selective 11β-HSD1 inhibitors are in development ( 11 ). (diabetesjournals.org)
- These results demonstrate an enzymatic origin of species differences in 7-oxysterol metabolism, establish the origin of endogenous 7beta-OH cholesterol in humans, and point to a possible involvement of 11beta-HSD1 in atherosclerosis. (ox.ac.uk)
- Corticosteroid 11-β-dehydrogenase isozyme 2 also known as 11-β-hydroxysteroid dehydrogenase 2 is an enzyme that in humans is encoded by the HSD11B2 gene. (wikipedia.org)
- The enzyme 11β-HSD1 is widely expressed and yields increased local tissue concentration of active glucocorticoid by converting cortisone into cortisol in humans, and 11-dehydrocorticosterone into corticosterone in rodents. (axonmedchem.com)
- We previously showed that carbenoxolone, an old drug that blocks multiple enzymes including 11beta-HSD1, improves memory in healthy elderly men and in patients with type 2 diabetes after just a month of treatment, so we are optimistic that our new compounds will be effective in humans. (qualitycounts.com)
- Selective 11beta-HSD1 inhibition decreases pSer(307) IRS1, increases pThr(308) Akt/PKB, and decreases lipogenic and lipolytic gene expression that may represent an important mechanism underpinning their insulin-sensitizing action. (ox.ac.uk)
- Incubation of beta-cells in the presence of 11-dehydrocorticosterone leads to a dose-dependent inhibition of insulin release, indicating cellular activation of 11-dehydrocorticosterone to the receptor ligand, further confirmed by reporter gene assays. (ox.ac.uk)
- The human gene for 11 beta-hydroxysteroid dehydrogenase. (wikipedia.org)
- Association studies between the HSD11B2 gene (encoding human 11beta-hydroxysteroid dehydrogenase type 2), type 1 diabetes mellitus and diabetic nep. (cdc.gov)
- Mutations in the HSD11B2 gene (encoding human 11beta-hydroxysteroid dehydrogenase type 2) explain the syndrome of apparent mineralocorticoid excess where cortisol acts as a mineralocorticoid. (cdc.gov)
- Weak associations are reported between the HSD11B2 gene, type 1 diabetes mellitus and nephropathy. (cdc.gov)
- Although the antiinflammatory activity of GCs is well described, there is also accumulating evidence that GCs are not only inhibitory, but may also enhance immune cell activation and induce gene transcription ( 10 , 11 ). (rupress.org)
- The mechanism of the variable and distinct 11β-hydroxysteroid dehydrogenase type 2 gene ( HSD11B2 ) expression in the cortical collecting duct is poorly understood. (ahajournals.org)
- A novel nonstop mutation in the stop codon and a novel missense mutation in the type II 3beta-hydroxysteroid dehydrogenase (3beta-HSD) gene causing, respectively, nonclassic and classic 3beta-HSD deficiency congenital adrenal hyperplasia. (wikipathways.org)
- Two homozygous mutations in the 11 beta-hydroxysteroid dehydrogenase type 2 gene in a case of apparent mineralocorticoid excess. (wikipathways.org)
- An important gene associated with Hyperandrogenism Due to Cortisone Reductase Deficiency is H6PD (Hexose-6-Phosphate Dehydrogenase/Glucose 1-Dehydrogenase). (malacards.org)
- Corticosteroid 11-β-dehydrogenase isozyme 2 is an NAD+-dependent enzyme expressed in aldosterone-selective epithelial tissues such as the kidney, colon, salivary and sweat glands. (wikipedia.org)
- We measured fat content by dual-energy X-ray absorptiometry and magnetic resonance imaging (MRI), liver fat by ultrasound and MRI, the hypothalamic-pituitary-adrenal axis by adrenal response to ACTH 1-24 , unconjugated urinary cortisol excretion, corticosteroid-binding globulin, and cortisol clearance by MS. We assessed insulin sensitivity by hyperinsulinaemic-euglycaemic clamp and by OGTT. (springer.com)
- Elevated local tissue glucocorticoid excess, driven by increased levels of the intracellular glucocorticoid regenerating enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), particularly in adipose tissue, is implicated in the development of idiopathic metabolic syndrome ( 3 ). (diabetesjournals.org)
- OBJECTIVE The cortisol-regenerating enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) amplifies glucocorticoid levels in liver and adipose tissue. (diabetesjournals.org)
- Cortisol levels in these tissues are amplified by the 11β-reductase activity of the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), which regenerates cortisol from inert cortisone ( 2 ). (diabetesjournals.org)
- In this paper, we examined the metabolic implications of curcumin, a compound known for its anti-inflammatory properties and inhibitory action on the enzyme 11β-HSD1, in a rodent model of adiposity rebound after the cessation of diet and exercise. (nih.gov)
- The enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) is selectively expressed in aldosterone target tissues, conferring aldosterone selectivity for the mineralocorticoid receptor. (ahajournals.org)
- In contrast, the enzyme 11β-HSD2 catalyzes the opposite reaction, the inactivation of active glucocorticoid. (axonmedchem.com)
- Furthermore, selective 11beta-HSD1 inhibition has been proposed as a novel therapeutic strategy in many of these conditions. (nih.gov)
- Here we review the role of 11beta-HSD1 in human disease and discuss the impact of selective 11beta-HSD1 inhibition. (nih.gov)
- Inhibition of 11β-HSD1 is viewed as a potential target for the treatment of obesity and other elements of the metabolic syndrome. (rcsb.org)
- Inhibition of 11beta-HSD activity by carbenoxolone reverses inhibition of insulin release. (ox.ac.uk)
- Inhibition of tissue-specific glucocorticoid activation by 11beta-HSD1 constitutes a promising target in the treatment of metabolic and cardiovascular diseases. (ox.ac.uk)
- The benefits of pharmacological inhibition may be reduced if hepatic 11β-HSD1 is similarly decreased in obese patients with type 2 diabetes. (diabetesjournals.org)
- The benzothiazole derivatives 1 and 2 showed greater than 80% inhibition for 11beta-HSD1 at 10 microM and exhibited IC50 values in the low micromolar range. (ox.ac.uk)
- Therefore, the inhibition of 11β-HSD1 is currently regarded as a promising therapeutic target [ 5 ]. (mdpi.com)
- For example, GCs potently inhibit the production of proinflammatory cytokines, such as TNFα, presumably through the inhibition of the transcription factors NFκB and AP-1 ( 7 ). (rupress.org)
- Selective inhibition of 11 beta-hydroxysteroid dehydrogenase type 1 improves hepatic insulin sensitivity in hyperglycemic mice strains. (axonmedchem.com)
- Acute inhibition of 11beta-hydroxysteroid dehydrogenase type-1 improves memory in rodent models of cognition. (discoverx.com)
- Benzothiazole derivatives as novel inhibitors of human 11beta-hydroxysteroid dehydrogenase type 1. (ox.ac.uk)
- Steroid biomarkers and genetic studies reveal inactivating mutations in hexose-6-phosphate dehydrogenase in patients with cortisone reductase deficiency. (malacards.org)
- Within skeletal muscle, 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) converts cortisone (11-dehydrocorticosterone in rodents) to active cortisol (corticosterone in rodents). (lenus.ie)
- 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)
- The presence of 11beta-HSD in islets supports the concept that reactivation of inert circulating hormone precursors in a cell-specific manner plays a major role in glucocorticoid physiology in rodents and man. (ox.ac.uk)
- In rodents, 11β-HSD1 is a powerful determinant of metabolic health. (diabetesjournals.org)
- Obese rodents exhibit tissue-specific dysregulation of 11β-HSD1, usually with upregulation in adipose tissue and downregulation in liver ( 6 , 7 ). (diabetesjournals.org)
- Although dietary energy restriction can increase the maximum lifespan of laboratory animals and is therefore hailed as an "antiaging" intervention ( 10 ), its major effect is to increase the average lifespan by preventing or delaying the development of various diseases that are the primary cause of death in overweight rodents ( 11 ). (pnas.org)
- In addition to being overweight, laboratory rodents maintained under standard laboratory conditions exhibit a physiological profile consistent with increased disease susceptibility, compared to animals maintained on lower energy diets and/or animals with higher physical activity levels (see Table 1 for overview). (pnas.org)
- 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)
- 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)
- 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)
- 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)
- Pancreatic islets isolated from ob/ob mice display type 1 11beta-hydroxysteroid dehydrogenase activity, i.e. in intact cells the reductive reaction prevails, leading from dehydrocorticosterone to corticosterone. (ox.ac.uk)
- Expression of type 1 11beta-HSD mRNA was detected by reverse transcriptase-polymerase chain reaction in islets isolated from ob/ob mice and also from human tissue. (ox.ac.uk)
- For example, transgenic mice selectively overexpressing 11β-HSD1 in adipose tissue develop obesity, insulin resistance, hypertension, and dyslipidemia ( 3 , 4 ). (diabetesjournals.org)
- Similarly, mice overexpressing 11β-HSD1 in the liver develop adverse metabolic features but do not become obese ( 5 ). (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)
- Indeed, simply reducing daily food intake 20-40% below the ad libitum amount, or providing food intermittently, rather than continuously, has been shown to significantly reduce the risk of developing diseases such as cancer, type 2 diabetes, and renal failure and can extend lifespan by up to 40% in rats and mice ( 3 , 6 , 7 ). (pnas.org)
- Laboratory mice and rats are typically housed either singly or in groups of 2-5 per cage with 1-3 square feet of floor space covered with bedding. (pnas.org)
- Importantly, genes belonging to steroid hormone biosynthesis (3 beta-hydroxysteroid dehydrogenase-1, cholesterol side-chain cleavage cytochrome P450, and steroid-11 beta-hydroxylase) were all expressed less in mice on a high-fat diet. (wur.nl)
- The importance of these immunoregulatory cytokines in the maintenance of immune homeostasis in the gut is illustrated by the fact that TGFβ and IL-10-deficient mice develop spontaneous inflammatory bowel disease (for review see reference 1 ). (rupress.org)
- Oxidative Medicine and Cellular Longevity , Vol. 2016, p. 1. (cambridge.org)
- 11β-Hydroxysteroid dehydrogenase type 1, also known as cortisone reductase, is an NADPH-dependent enzyme highly expressed in key metabolic tissues including liver, adipose tissue, and the central nervous system. (wikipedia.org)
- Biochemical and pharmacogenetic dissection of human steroid 5 alpha-reductase type II. (wikipathways.org)
- At a tissue specific level, the enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) locally regenerates active cortisol from inactive cortisone amplifying glucocorticoid receptor activation in the context of normal circulating cortisol levels. (nih.gov)
- Whereas the type 1 enzyme (11beta-HSD1) is in vitro a NADP(H)- dependent bidirectional enzyme, it reduces in most instances in vivo cortisone to active cortisol. (ox.ac.uk)
- 11beta-Hydroxysteroid dehydrogenase type 1 (11beta-HSD1) is an intraluminally oriented, endoplasmic reticulum (ER)-bound enzyme catalyzing the interconversion between inactive cortisone and hormonally active cortisol. (ox.ac.uk)
- Biochemical studies indicated a decreased rate of conversion of active cortisol to cortisone, and the authors postulated a defect in 11-beta-hydroxy oxidation of cortisol. (steroids-australia.net)
- Elevenbeta-hydroxysteroid dehydrogenase type 1 (11beta-HSD-1), a key intracellular enzyme which catalyses the conversion of inactive cortisone to active cortisol, has been implicated in the development of the metabolic syndrome. (unimi.it)
- The increased frequency of HSD11B2 short alleles in the diabetic groups may reflect reduced renal 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) activity and may, in part, explain the enhanced salt sensitivity observed in patients with type 1 diabetes. (cdc.gov)
- 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)
- To examine this, we quantified in vivo whole-body, splanchnic, and hepatic 11β-HSD1 activity in obese type 2 diabetic subjects. (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)
- 14. The method of claim 1, wherein EAAT2 protein expression is increased in vivo. (freepatentsonline.com)
- Kiran SG, Dorisetty RK, Umrani MR, Boindala S, Bhonde RR, Chalsani M, Singh H, Venkatesan V (2011) Pyridoxal 5′ phosphate protects islets against streptozotocin-induced beta-cell dysfunction-in vitro and in vivo. (springer.com)
- Duration of type 1 diabetes, diabetic status and renal function were recorded. (cdc.gov)
- Further, the expression of leptin and 11 β-hydroxysteroid dehydrogenase 1 genes were significantly increased in CrR offspring of both the sexes. (pubmedcentralcanada.ca)
- RESEARCH DESIGN AND METHODS Ten obese men with type 2 diabetes and seven normal-weight control subjects were infused with 9,11,12,12-[ 2 H] 4 cortisol (40%) and cortisol (60%) at 1.74 mg/h. (diabetesjournals.org)
- This supports the concept that inhibitors of 11β-HSD1 are likely to be most effective in obese type 2 diabetic subjects. (diabetesjournals.org)
- According to the US National Commission on Diabetes, the likelihood of acquiring type 2 diabetes is 2-fold for mildly obese individuals, 5-fold for moderately obese individuals, and 10-fold for the severely obese individuals (Pi-Sunyer, 2007). (kon.org)
- 1 The 2008 World Health Organization statistics indicated that ≈1.5 billion adults are overweight, of which 200 million men and 300 million women were classed as obese, a figure predicted to rise by 50% by 2015. (ahajournals.org)
- Substantial extra-adrenal regeneration of cortisol by 11β-HSD1 has been detected in the splanchnic circulation ( 13 , 14 ), arising mainly from liver ( 15 , 16 ), and in subcutaneous adipose tissue ( 15 ). (diabetesjournals.org)
- In this study, we determined the role of glucocorticoid conversion by 11beta-HSD in pancreatic islets and its function in the regulation of insulin release. (ox.ac.uk)
- The recent development of specific 11beta-HSD1 inhibitors coupled with advances on structural knowledge and regulation of the 11beta-HSD1 target has undoubtedly promoted the understanding of glucocorticoid control of metabolic regulation. (ox.ac.uk)
- In the attempt to control the rise of type 2 diabetes, new treatments such as these 11β-HSD1 inhibitors and others that focus on mechanisms relating to cortisol regulation may have favorable results. (kon.org)
- Likewise, models of estrogen insufficiency have unveiled new and unexpected roles for estrogens, in both males and females, many of which apply to the regulation of energy homeostasis [ 11 , 12 ]. (hindawi.com)
- Lipid G protein-coupled receptor ligand identification using beta-arrestin PathHunter assay. (discoverx.com)
- Effects of peroxisome proliferator-activated receptor-alpha and -gamma agonists on 11beta-hydroxysteroid dehydrogenase type 1 in subcutaneous adipose tissue in men. (ox.ac.uk)
- Selective 11β-HSD1 inhibitors are efficacious in several rodent models of diabetes ( 8 - 11 ). (diabetesjournals.org)
- In our efforts to prepare potent and selective 11β-HSD1 inhibitors based on a pharmacophore structure designed in silico by the Lagos group, we set out to synthesize several 3,5-disubstituted 1,2,4-oxadiazole derivatives. (mdpi.com)
- 11Beta-hydroxysteroid dehydrogenase type 1 in human disease: a novel therapeutic target. (nih.gov)
- 11beta-HSD1 activity and expression were observed in human and rodent myotubes and muscle explants. (ox.ac.uk)
- 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)
- 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)
- Here, we report the discovery and synthesis of a series of novel benzothiazole derivatives and their inhibitory activities against 11beta-HSD1 from human hepatic microsomes measured using a radioimmunoassay (RIA) method. (ox.ac.uk)
- Docking studies with the benzothiazole derivative 1 into the crystal structure of human 11beta-HSD1 revealed how the molecule may interact with the enzyme and cofactor. (ox.ac.uk)
- We report here on the in vitro oxysterol-metabolizing properties of human and rodent 11beta-HSD1. (ox.ac.uk)
- 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)
- The human GR is a modular protein composed of distinct regions illustrated in panel B in the image below, as follows: (1) The amino-terminal A/B region, also called immunogenic or N-terminal domain (NTD) and (2) the C, D, and E regions, which correspond to the DNA-binding domain, the hinge region, and the ligand-binding domain, respectively. (medscape.com)
- 17β-Oestradiol promotes differentiation of human embryonic stem cells into dopamine neurons via cross-talk between insulin-like growth factors-1 and oestrogen receptor β. (bl.uk)
- Cortisol acts as an antagonist of insulin action, and 11beta-HSD1 mediated production of cortisol has been hypothesized to contribute to human insulin resistance and type 2 diabetes. (drugbank.ca)
- Bord S, Horner A, Beavan S, Compston J. Estrogen receptors alpha and beta are differentially expressed in developing human bone. (labome.org)
- The translational efficacy of a nonsteroidal progesterone receptor antagonist, 4-[3-cyclopropyl-1-(mesylmethyl)-5-methyl-1H-pyrazol-4-yl]oxy,-2,6-dimethylbenzonitrile (PF-02413873), on endometrial growth in macaque and human. (discoverx.com)
- 2. The method of claim 1, wherein the subject is a human. (freepatentsonline.com)
- Enasidenib drives human erythroid differentiation independently of isocitrate dehydrogenase 2. (stanford.edu)
- Type 2 diabetes mellitus (T2DM) is a metabolic disease associated with insulin resistance and pancreatic β-cell failure ( Defronzo, 2009 ). (peerj.com)
- 11β-HSD1 is also found in pancreatic islets ( 4 ). (diabetesjournals.org)
- Type 1 11beta -hydroxysteroid dehydrogenase mediates glucocorticoid activation and insulin release in pancreatic islets. (ox.ac.uk)
- Investigated for use/treatment in diabetes mellitus type 2 and diabetes prevention. (drugbank.ca)
- although the morbidity and mortality rates for countless diseases have been reduced due to advances in medical research and high standard of living, the rate of type 2 diabetes mellitus increases. (kon.org)
- The latter effect is accomplished by two different 11beta-hydroxysteroid dehydrogenase isozymes, constituting a shuttle system between the receptor ligand cortisol and its non-binding precursor cortisone. (ox.ac.uk)
- Interconversion between cortisone and the glucocorticoid receptor ligand cortisol is carried out by 11beta-hydroxysteroid dehydrogenase (11beta-HSD)isozymes and constitutes a medically important example of pre-receptor control of steroid hormones. (ox.ac.uk)
- The most important reaction for this class of steroids is the reversible C11 keto/beta-hydroxyl conversion between receptor-binding 11beta-OH steroids and the nonbinding 11-oxo compounds, carried out by 11beta-hydroxysteroid dehydrogenases (11beta-HSDs). (ox.ac.uk)
- 13. The method as in any one of claims 1 , 5 or 8 , wherein the cannabidiol derivative compound of the pharmaceutical composition is further combined with one or more anti-inflammatory compounds or immunomodulatory drugs. (freepatentsonline.com)
- The invention concerns 4-aminomethyl-1-aryl-cyclohexylamine compounds, methods for producing same, pharmaceutical formulations containing said compounds and the. (patents.com)
- This invention comprises the compounds of formula (I): ##STR00001## wherein r, s, t, Y.sup.1 Y.sup.2, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6 and. (patents.com)
- Compounds bind to and activate ADRENERGIC BETA-2 RECEPTORS. (drugbank.ca)
- Described herein are methods of treating or preventing neurological disease and disease symptoms using beta-lactam compounds, and compounds useful for treating disease and disease symptoms. (freepatentsonline.com)
- PATIENTS AND PARTICIPANTS: Healthy men and patients with type 2 diabetes participated. (ox.ac.uk)
- [ 12 ] In a study of 190 patients with type 2 diabetes, 63 subjects (33%) had high cortisol concentrations. (medscape.com)
- INCB13739 inhibits 11beta-HSD1 and has the potential to provide a broad spectrum impact on the multiple components seen in patients with type 2 diabetes. (drugbank.ca)
- We have investigated the effects of fetal growth restriction, induced by restriction of placental growth and function (PR), on 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD-1) and 11betaHSD-2 messenger RNA (mRNA) expression in fetal tissues in the sheep, using Northern blot analysis. (edu.au)
- If confirmed, these results would prompt the development of selective and tissue-specific 11beta-HSD-1 inhibitors to decrease insulin resistance and treat the metabolic syndrome, thus contrasting the harmful effects of glucocorticoid excess in peripheral tissues. (unimi.it)
- this evidence of increased mineralocorticoid activity was associated with increased aldosterone metabolites and decreased 11β-hydroxysteroid dehydrogenase type 2 activity. (whiterose.ac.uk)
- 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)
- G6P availability directly modulates the activity of 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1), an ER-bound enzyme playing a key role in the development of the metabolic syndrome (MS). (biomedcentral.com)
- In 12 healthy men, 4-5 wk of rosiglitazone increased insulin sensitivity during insulin infusion but did not change 11beta-HSD1 mRNA or activity in sc adipose tissue, and insulin sensitization was unaffected by glucocorticoid blockade with a combination of metyrapone and RU38486. (ox.ac.uk)
- Enzyme activity has been quantified using a stable isotope tracer, 9,11,12,12-[ 2 H] 4 cortisol (d4-cortisol), from which the 11-deuterium is removed during interconversion with cortisone, allowing quantification of dilution of d4-cortisol by d3-cortisol and hence of 11β-HSD1 activity, independently from the influence of other cortisol-metabolizing enzymes ( 12 ). (diabetesjournals.org)
- 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)
- We investigated the effect of curcumin, a naturally occurring polyphenol known for its anti-inflammatory properties and inhibitory action on 11β-HSD1 activity, on preserving metabolic health and limiting adipose tissue growth following the cessation of daily exercise and caloric restriction (CR). (nih.gov)
- Our study suggests that emodin inhibits DPP4 activity and may represent a novel therapeutic for the treatment of type 2 diabetes. (peerj.com)
- These findings have immediate significance for current therapeutic strategies for type 2 diabetes. (diabetesjournals.org)
- Could the natural compound emodin, which inhibits DPP4 protein, be new therapeutic for treatment of type 2 diabetes? (peerj.com)
- 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)
- INCB13739 completely inhibits the production of intra-adipose and intra-hepatic cortisol by 11beta-HSD1, while maintaining normal systemic cortisol levels, which are essential for immune function and response to stress. (drugbank.ca)
- Increased rates of co-morbidities such as type 2 diabetes and hepatic damage in overweight adolescents indicate that the young are not protected from the metabolic perturbations that accompany excess adipose tissue stores. (nih.gov)
- In 12 men with type 2 diabetes 12 wk of rosiglitazone reduced arteriovenous cortisone extraction across abdominal sc adipose tissue and reduced 11beta-HSD1 mRNA in sc adipose tissue but increased plasma cortisol concentrations. (ox.ac.uk)
- Alternative splicing of the primary transcript gives rise to the 2 mRNA and protein isoforms, hGR-alpha and hGR-beta. (medscape.com)
- There was also an approximately 2-fold increase in the ratio of 11betaHSD-1 mRNA/18S rRNA expression in the PR group (53.8+/-7.9) compared with that in control animals at 141-145 days gestation. (edu.au)
- Specific inhibitors against the type 1 enzyme lower intracellular levels of glucocorticoid hormone, with an important clinical application in insulin resistance and other metabolic disorders. (ox.ac.uk)