TMT-based Quantitative Proteomic Study Of Neonatal Diabetes Mellitus Via Kir6.2CA Zebrafish Model

Diabetes mellitus(DM)is a group of metabolic disorders in which there are high blood sugar levels.Diabetes is due to either the pancreas not producing enough insulin or the cells of the body not responding properly to the insulin produced.Neonatal diabetes mellitus(NDM)is a kind of diabetes that occurs in the first 6 months of life.There are two types of NDM:permanent neonatal diabetes mellitus(PNDM)is a lifelong condition.Transient neonatal diabetes mellitus(TNDM)is diabetes that disappears during the infant stage but may reappear later in life.NDM can be easily mistaken for the type 1 diabetes then be less likely to catch diabetes at a more treatable stage or select the wrong treatment methods.The pathogenesis of NDM still unconfirmed because of the absence of clinical cases.It's emergency to find out molecular marker and investigate the mechanism of NDM.The Zebrafish(Danio rerio)is an important and widely used vertebrate model organism in scientific research since zebrafish have genetic homogeneity with human in 87%percentage,share basically the same signaling pathways.Zebrafish and mammal have highly similar physiology and body functions.The zebrafish embryo develops rapidly so could reducing breeding cycle times.The pancreas and peripheral tissue which sensibility to insulin of zebrafish are highly conserved during evolution,therefore zebrafish and mammal share high similar mechanisms.Above all,zebrafish is an elegant diabetes model.In this thesis,TMT-based quantitative proteomics approach was used to compare the proteome between wild-type zebrafish and Kir6.2CA NDM model zebrafish.We found that the insulin secretive function was down-regulated in Kir6.2CA group.Glycolysis pathway,lipid transport activity and oxidative phosphorylation activity in which involved oxidative stress were enhanced in Kir6.2CA group.The extracellular matrix receptor interaction activity and Solute carrier function were weakened in Kir6.2CA group.Besides,ribosomes proteins change a lot between wild type group and Kir6.2CA group.These result therefore provide useful information for further investigations on the mechanism of NDM and discovery of molecular marker for the NDM.Beyond that,we hope that our research will provide additional insight into the mechanism and treatment of type 2 diabetes.