Effect And Mechanism Of Nesfatin-1 On The Ferroptosis Of Pancreatic β Cell And Clinical Application

Background:Type 2 diabetes mellitus(T2DM)is a kind of abnormal glucose metabolism disease,which is complicated and complicative and causes serious damage to patients’ physical and mental health,insulin resistant and β cell dysfunction are main causes of T2 DM.Nesfatin-1 is a functional polypeptide which could act as antioxidant and anti-inflammatory.Aim:We aim to explore the role and mechanism of nesfatin-1 in ferroptosis in pancreatic β cell through basic experiments,and we also explore whether serum nesfatin-1 levels could protect the insulin secretion function of pancreatic β cell in the development of T2 DM.Materials and methods:We detected the proliferation and vitality of MIN6 cell through MTT,CCK-8 and crystal violet staining.The levels of GPX4,GSH,SOD,MDA and ROS were tested to reflect the antioxidant ability of MIN6 cell.The submicroscopic structure of MIN6 was gotten via electron transmission microscope.Insulin secretion level was examined by ELISA to mirror the MIN6 cell insulin secretion under sugar stimulates,intracellular iron content was detected with spectrophotometry and SLC40A1 and FTH1 levels were detected by q PCR and western blot.We recruited 75 T2 DM patients,67 prediabetes patients and 37gender-age matched healthy control and detected serum nesfatin-1 levels with ELISA,and statistical analysis the variation and correlation with insulin secretion of serum nesfatin-1 levels.Results:MIN6 cell proliferation,vitality and antioxidant ability decreased when treat with RSL3,and the mitochondria exhibit mitochondrial abnormalities such as condensation,increased membrane density,reduced or absent crista.Insulin secretion under sugar stimulates and SLC40A1 and FTH1 expression on protein level were significantly decreased after RSL3 treatment.However,intracellular iron content and the m RNA levels of SLC40A1 and FTH1 were obviously elevated.Meanwhile,preincubated MIN6 cell with nesfatin-1,the decreased proliferation,vitality,antioxidant ability,insulin secretion and protein SLC40A1 and FTH1 of MIN6 cell could be reversed,elevated intracellular iron content and m RNA levels of SLC40A1 and FTH1 also could be downregulated.Serum nesfatin-1 levels significantly decreased in the development from health(1060.43±823.72 pg/ml)to T2DM(622.94±218.28 pg/ml)via prediabetes(875.88±578.71 pg/ml).Meanwhile,serum nesfatin-1levels exhibited obviously correlated(r=0.6342)with insulin secretion.Conclusion:Nesfatin-1 through upregulating iron excretion and storage to protect the function of pancreatic β cell from ferroptosis,serum nesfatin-1 levels significantly decreased in the development from health to T2 DM via prediabetes and obviously correlated with insulin secretion.