11beta-Hydroxysteroid dehydrogenase type 1 inhibitors: novel agents for the treatment of metabolic syndrome and obesity-related disorders?

Anagnostis, Panagiotis; Katsiki, Niki; Adamidou, Fotini; Athyros, Vasilios G.; Karagiannis, Asterios; Kita, Marina; Mikhailidis, Dimitri P.

doi:10.1016/j.metabol.2012.05.002

Cited by 87 publications

(70 citation statements)

References 111 publications

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“…Older non-selective 11β-HSD-1 inhibitors such as liquorice and its active metabolite glycyrrhizic and glycyrrhetinic acids inhibit both 11β-HSD-1 and 11β-HSD-2 enzymes [29] . Ingesting liquorice and glycyrrhizic or glycyrrhetinic acids have been shown to produce a type of "mineralocorticoid excess" syndrome, hypertension encephalopathy, and hypokalemic paralysis [29] .…”

Section: Non Selective 11β-hsd-1 Inhibitorsmentioning

confidence: 99%

Section: Non Selective 11β-hsd-1 Inhibitorsmentioning

confidence: 99%

“…Ingesting liquorice and glycyrrhizic or glycyrrhetinic acids have been shown to produce a type of "mineralocorticoid excess" syndrome, hypertension encephalopathy, and hypokalemic paralysis [29] . It can also cause weight loss, sodium retention, potassium loss, and hypertension through the inhibition of 11β-HSD-2 [29] . Carbenoxolone, a non-selective 11β-HSD-1 inhibitor and product of liquorice reduces glucose concentrations and increases weight loss; inhibits hepatic triglyceride production, inhibits lipolysis, and increase HDL-C levels, but also causes sodium retention, potassium loss, and hypertension by inhibiting 11β-HSD-2 [29] .…”

Section: Non Selective 11β-hsd-1 Inhibitorsmentioning

confidence: 99%

“…It can also cause weight loss, sodium retention, potassium loss, and hypertension through the inhibition of 11β-HSD-2 [29] . Carbenoxolone, a non-selective 11β-HSD-1 inhibitor and product of liquorice reduces glucose concentrations and increases weight loss; inhibits hepatic triglyceride production, inhibits lipolysis, and increase HDL-C levels, but also causes sodium retention, potassium loss, and hypertension by inhibiting 11β-HSD-2 [29] . Vitamin A enriched diets also decrease fat and improve insulin sensitivity in animals and humans as it may inhibit 11β-HSD-1 and mRNA [29] .…”

Section: Non Selective 11β-hsd-1 Inhibitorsmentioning

confidence: 99%

“…Vitamin A enriched diets also decrease fat and improve insulin sensitivity in animals and humans as it may inhibit 11β-HSD-1 and mRNA [29] . These non-selective agents were evaluated in small trials with short durations [29] . Several 11β-HSD-1 inhibitors have been developed and are being tested for patients with obesity and diabetes, including INCB013739, MK0916, PF915275, AMG221 produced by a variety of manufacturers.…”

Section: Non Selective 11β-hsd-1 Inhibitorsmentioning

confidence: 99%

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Novel and emerging diabetes mellitus drug therapies for the type 2 diabetes patient

Rochester

Akiyode

2014

WJD

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Type 2 diabetes mellitus is a metabolic disorder of deranged fat, protein and carbohydrate metabolism resulting in hyperglycemia as a result of insulin resistance and inadequate insulin secretion. Although a wide variety of diabetes therapies is available, yet limited efficacy, adverse effects, cost, contraindications, renal dosage adjustments, inflexible dosing schedules and weight gain significantly limit their use. In addition, many patients in the United States fail to meet the therapeutic HbA1c goal of < 7% set by the American Diabetes Association. As such new and emerging diabetes therapies with different mechanisms of action hope to address some of these drawbacks to improve the patient with type 2 diabetes. This article reviews new and emerging classes, including the sodium-glucose cotransporter-2 inhibitors, 11β-Hydroxysteroid dehydrogenase type 1 inhibitors, glycogen phosphorylase inhibitors; protein tyrosine phosphatase 1B inhibitors, G Protein-Coupled receptor agonists and glucokinase activators. These emerging diabetes agents hold the promise of providing benefit of glucose lowering, weight reduction, low hypoglycemia risk, improve insulin sensitivity, pancreatic β cell preservation, and oral formulation availability. However, further studies are needed to evaluate their safety profile, cardiovascular effects, and efficacy durability in order to determine their role in type 2 diabetes management.© 2014 Baishideng Publishing Group Inc. All rights reserved.Key words: Type 2 diabetes mellitus; Sodium dependent glucose co-transporter 2 inhibitors; 11β-Hydroxysteroid dehydrogenase type 1 inhibitors; Glycogen phosphorylase inhibitors; Protein tyrosine phosphatase 1B inhibitors; G protein-coupled receptor agonists; Glucokinase activators Core tip: Type 2 diabetes mellitus is a metabolic disorder of deranged fat, protein and carbohydrate metabolism resulting in hyperglycemia. Limited efficacy, adverse effects, cost, contraindications, renal dosage adjustments, inflexible dosing schedules and weight gain significantly limit the use of currently available anti-hyperglycemic agents. In the past, drug researchers targeted defects of pancreatic β-cell failure and insulin resistance, but more recent attention has shifted to other contributing factors. This article reviews new and emerging diabetes classes, including the sodium-glucose cotransporter-2 inhibitors, 11β-Hydroxysteroid dehydrogenase type 1 inhibitors, glycogen phosphorylase inhibitors, protein tyrosine phosphatase 1B inhibitors, G protein-coupled receptor agonists, and glucokinase activators.

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Section: Non Selective 11β-hsd-1 Inhibitorsmentioning

confidence: 99%

Section: Non Selective 11β-hsd-1 Inhibitorsmentioning

confidence: 99%

Section: Non Selective 11β-hsd-1 Inhibitorsmentioning

confidence: 99%

Section: Non Selective 11β-hsd-1 Inhibitorsmentioning

confidence: 99%

Section: Non Selective 11β-hsd-1 Inhibitorsmentioning

confidence: 99%

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Novel and emerging diabetes mellitus drug therapies for the type 2 diabetes patient

Rochester

Akiyode

2014

WJD

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Celastrol attenuates high‐fructose diet‐induced inflammation and insulin resistance via inhibition of 11β‐hydroxysteroid dehydrogenase type 1 activity in rat adipose tissues

et al. 2021

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High fructose consumption has been linked to low-grade inflammation and insulin resistance that results in increased intracellular 11ß-hydroxysteroid dehydrogenase type 1 (11β-HSD1) activity. Celastrol, a pentacyclic triterpene, has been demonstrated to exhibit multifaceted targets to attenuate various metabolic diseases associated with inflammation. However, the underlying mechanisms by which celastrol exerts its attributive properties on high fructose diet (HFrD)-induced metabolic syndrome remain elusive. Herein, the present study was aimed to elucidate the mechanistic targets of celastrol co-administrations upon HFrD in rats and evaluate its potential to modulate 11β-HSD1 activity. Celastrol remarkably improved glucose tolerance, lipid profiles, and insulin sensitivity along with suppression of hepatic glucose production. In rat adipose tissues, celastrol attenuated nuclear factor-kappa B (NF-κB)-driven inflammation, reduced c-Jun Nterminal kinases (JNK) phosphorylation, and mitigated oxidative stress via upregulated genes expression involved in mitochondrial biogenesis. Furthermore, insulin signaling pathways were significantly improved through the restoration of Akt phosphorylation levels at Ser473 and Thr308 residues. Celastrol exhibited a potent, selective and specific inhibitor of intracellular 11β-HSD1 towards oxidoreductase activity (IC 50 value = 4.3 nM) in comparison to other HSD-related enzymes. Inhibition of 11β-HSD1 expression in rat adipose microsomes reduced the availability of its cofactor NADPH and substrate H6PDH in couple to upregulated mRNA and protein

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Protostane‐Type Triterpenoids from Alisma orientale

Chen

Luo

et al. 2017

Chemistry & Biodiversity

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Twenty-eight protostane triterpenoids, including a new degraded one (1), nine new ones (2 - 10), and two new natural ones (11 and 12), have been isolated from the dried rhizomes of Alisma orientale. Alisol R (1) was the first 20,21,22,23,24,25,26,27-octanorprotostane triterpenoid. The absolute configurations of 25-methoxyalisol F (2) and 16β-hydroperoxyalisol B 23-acetate (3) were determined by X-ray diffraction analysis. In addition, alismaketone-B 23-acetate (28) showed potent vasorelaxant activity on endothelium-intact thoracic aorta rings precontracted with KCl.

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11beta-Hydroxysteroid dehydrogenase type 1 inhibitors: novel agents for the treatment of metabolic syndrome and obesity-related disorders?

Cited by 87 publications

References 111 publications

Novel and emerging diabetes mellitus drug therapies for the type 2 diabetes patient

Novel and emerging diabetes mellitus drug therapies for the type 2 diabetes patient

Celastrol attenuates high‐fructose diet‐induced inflammation and insulin resistance via inhibition of 11β‐hydroxysteroid dehydrogenase type 1 activity in rat adipose tissues

Protostane‐Type Triterpenoids from Alisma orientale

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