Study On The Mechanism Underlying MSMB Inducing Gestational Diabetes Mellitus

Gestational diabetes mellitus(GDM)is defined as any degree of glucose intolerance with onset or first recognition during pregnancy.GDM threatens the health of both mothers and their offsprings.It not only leads to unfortunate outcome of gestation,but also results in increased risk of metabolic diseases such as type 2 diabetes in mothers and their offspring.Thus,GDM creates huge economic and psychological burden of whole society.As the living habits of Chinese people,the incidenc e of GDM in China is higher than global average.More importantly,the second-child policy will sharply increase the number of GDM patients in China,which indicated that improving the prevention and therapeutic therapy of GDM is important for Chinese researcher.There are two limitations in current diagnosis and treatment of GDM.First,no early screening methods are available.So far,GDM detection is relay on glucose test.While it will be too late to early prevention.Second,the therapeutic strategy is limited for GDM as our understanding about the pathology of GDM is not good enough for identification of drug target.Thus,improvement of our understanding about the molecular pathology of GDM is important for development of its novel diagnostic and therapeutic strategies.We know that pregnant women induce physiological insulin resistance to save blood sugar for fetal development.Therefore,we assume that there are some factors secreted by reproductive organs of pregnant women contributes to the regulation of insulin sensitivity of peripheral cells.And dysregulation of the secretion of these factors induces GDM.In this study,we first drew the tear proteomic profile of normal women,normal pregnant women,and GDM pregnant women to identify candidate proteins that were differentially expressed in the tears of pregnant and GDM women.We found MSMB is a candidate subject that is upregulated in pregnant women and is abnormally upregulated in GDM women.This result was further confirmed by Elisa assay with human blood.Through immunohistochemistry experiments,we found that MSMB was expressed in placental cells and a significant difference of the expression level of MSMB in placental cells was found between normal pregnant women and GDM pregnant women.Finally,we demonstrated the regulatory role of MSMB on insulin sensitivity of adipocytes and muscle cells by cell-based assay.Taken together,these results demonstrated that MSMB as a secreted protein that can induces physiological insulin resistance during pregnant and can leads to GDM when it is dysregulated.In summary,this work reveals a novel molecular mechanism of glucose metabolism regulation during pregnancy and a novel pathological mechanism of GDM.This study suggests a novel therapeutic strateg y for GDM.