The Molecular Mechanism Of SNAPIN Regulating The Growth Of Islet β Cells

Diabetes Mellitus is the most common metabolic disease and metabolic syndrome.The main pathological features are associated with peripheral hyperglycemia that is caused by reduced insulin secretion or defective action.Quality or quantity of islet β cells loss leads to insulin production reducing,and islet β cells undergo apoptosis or functional failure during the development of diabetes.The main therapy method to cure diabetes is to increase insulin level,including insulin injection and oral hypoglycemic drugs et al.At present,the treatment to increase insulin secretion by increasing the number of β cells is facing great challenges.SNAPIN,also known as SNAP-25 binding protein,is one of the family members of the BLOC-1 complex and the BORC complex.SNAPIN was originally found as a SNAP-related protein involved in synaptic transmission,and it is highly expressed in neurons.SNAPIN directly interacts with SNAP-25 that is associated with the SNARE complex,which is involved in the transport and delivery of neuronal vesicles,plasma membrane fusion and exocytosis,and it also plays the role of neurotransmitter synapse transmission information and Ca2+regulated neurotransmitter secretion.The insulin secretion is a process of vesicle transport of insulin particles,which mainly includes targeting,aggregation,initiation and membrane fusion of insulin particles.SNAPIN can participate in the process of insulin vesicle transport and play the role in regulating insulin secretion.The dissertation found that the expression of SNAPIN in diabetic and prediabetic mice was lower than that in normal mice.Next,the overexpressed SNAPIN in mouseβ cell promotes cell growth and increases insulin secretion,knockdown of SNAPIN in mouse β cell can decrease cell growth and reduce insulin secretion.SNAPIN increases pancreatic β cells growth by stimulating insulin secretion because the insulin is well-known for cell growth hormone.However,the results also reveal that SNAPIN promotes pancreatic β cells growth by possible interacting with cell cycle associated proteins becasuse of SNAPIN and interaction of protein mass spectrometry data enrichment in the access of the cell cycle,then the further testing found that SNAPIN can affect the expression of cell cycle associated protein CDK2、CDK4 et al.