The Study Of Function And Mechanism Of Stearoyl-CoA Desaturase 1 In Pancreatic β Cells

Stearoyl-CoA desaturase 1(SCD1),which mainly locates in the membrane of the endoplasmic reticulum,plays an important role in the regulation of lipid metabolism and insulin sensitivity.It has been reported that in the systemic SCD1(-/-)knockout ob/ob mouse,though the insulin sensitivity has been strongly ameliorated,the failure of the islets occurred performing a serious shortage of synthesis and secretion of insulin[1].While the molecular mechanism is not clear,this study is aim to explore the effect of SCD1 in the function and survival of the pancreatic β cells as well as the related regulatory mechanisms.First of all,in the rat INS-1β cells,we silenced the expression of SCD1 by siRNA,and then test the KSIS and insulin content of the cells.The results shows,silencing SCD1 in the INS-1 cells make the KSIS and the insulin content decline.Then,we test the expression level of specific transcription factors in the INS-1 cells when overexpressing or silencing SCD1.The results shows,the protein level of MafA significantly increases by overexpressing SCD1 while decreases by silencing SCD1.However there is on change of the mRNA level of MafA.Furthermore,we have found that SCD1 can interact with MafA through its histidine box so that to avoid the degradation of MafA thereby strengthening the protein stability of MafA.Pathological stimuli,such as Tm or Inflammatory cytokines IL-1β,can decrease the protein level of both SCD1 and MafA in a concentration dependent manner when acting on INS-1 cells.Moreover,the decrease of the protein level of MafA by Tm or IL-1β can be reversed by overexpressing SCD1.IL-1β not only weakened the interaction between SCD1 and Maf A,but also augmented the ubiquitination of MafA.Additionally,overexpression of SCD1 was able to not only reduce the ubiquitination of MafA partially,but to reverse the KSIS function as well as the insulin content of INS-1 cells caused by IL-1β.In summary,this study reveals that SCD1 can enhance the protein stability of MafA through the interaction under the basal condition.Moreover,when β cells were exposed to some pathological stimuli,the ubiquitination of MafA increased due to the interaction between SCD1 and MafA weakend leading to the protein stability of MafA declined resulting in the dysfunction of β cells.This study enriches the cognition of biological function of SCD1 in the β cells and provides the new therapeutic targets and theoretical basis for the treatment of diabetes mellitus.