English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) controls the production of active glucocorticoid (GC) and has been proposed as a new target for the treatment of type 2 diabetes. We have previously reported that a natural product, curcumin, exhibited moderate inhibition and selectivity on 11β-HSD1. By analyzing the models of protein, microsome, cells and GCs-induced mice in vitro and in vivo , this study presented a novel curcumin analog, LG13, as a potent selective 11β-HSD1 inhibitor. In vivo , Type 2 diabetic mice were treated with LG13 for 42 days to assess the pharmacological benefits of 11β-HSD1 inhibitor on hepatic glucose metabolism. In vitro studies revealed that LG13 selectively inhibited 11β-HSD1 with IC 50 values at nanomolar level and high selectivity over 11β-HSD2. Targeting 11β-HSD1, LG13 could inhibit prednisone-induced adverse changes in mice, but had no effects on dexamethasone-induced ones. Further, the 11β-HSD1 inhibitors also suppressed 11β-HSD1 and GR expression, indicating a possible positive feedback system in the 11β-HSD1/GR cycle. In type 2 diabetic mice induced by high fat diet plus low-dosage STZ injection, oral administration with LG13 for 6 weeks significantly decreased fasting blood glucose, hepatic glucose metabolism, structural disorders, and lipid deposits. LG13 exhibited better pharmacological effects in vivo than insulin sensitizer pioglitazone and potential 11β-HSD1 inhibitor PF-915275. These pharmacological and mechanistic insights on LG13 also provide us novel agents, leading structures, and strategy for the development of 11β-HSD1 inhibitors treating metabolic syndromes.

Inhibition of 11β-HSD1 by LG13 improves glucose metabolism in type 2 diabetic mice