ABSTRACT
[Summary] MS ,which is highly related tothe occurrence of cardiovascular disease and T2DM ,is characterized by glucose and fat metabolic dysregulation ,central obesity ,hypertension and hyperuricemia.11β‐hydroxysteroid dehydrogenase type 1 (11β‐HSD1) is regarded as a new therapeutic target for MS.11β‐HSD1 converts inactive glucocorticoid to active glucocorticoid. 11β‐HSD1 knockout improves obesity , hyperlipidemia andhyperglycemia. The inhibition of 11β‐HSD1 alleviates IR in human and rodents ,but the application of 11β‐HSD1 inhibitors is limited by the side effects.
ABSTRACT
Objective To investigate the effect of small interference RNA (siRNA) targeting at 11β-hydroxysteroid dehydrogenase type 1 on the glucose-stimulated insulin secretion (GSIS) in pancreatic β cell line NIT-1 cell.Methods siRNA plasmid vectors specifically targeting at 11β-HSD1 gene were constructed,named as olig886,oligo866 and scrabble control for oligo886,then tansfected into NIT-1 cells.The expression of 11β-HSD1 was detected by RT-PCR and Western blot.O1igo886 vector was transfected into the NIT-1 cells in 25 mmol/L glucose concentrations medium.The insulin secretion level was measured in GSIS test.Results After treatment with 11β-HSD1 siRNA,the mRNA level of 11β-HSD1 in NIT-1 cell was decreased by 78.1%±2.9% and 51.7% ±2.7% inolig886 and oligo866 group respectively.The protein of 11β-HSD1 were decreased by 82.2% ±2.1% and 56.5%±2.0 % respectively.After transfected by olig 8 8 6 vector,the insulin secretion increased in NIT -1 cell.Conclusion 11β-HSD1 gene silencing may improve GSIS in NIT-1 cell 11β-HSD1 regulate local glucocorticoid metabolism in pan-creatic islet and affect the function of insulin secretion.