Effects Of Adaptor Proteins On Regulation Of Pancreatic Beta-cells

Objective The reduction of pancreatic beta-cell mass plays an important role in the development of diabetes.The aims of the present study were 1)to establish an in vivo tracking platform for pancreatic beta-cell mass through the use of non-invasive bioluminescence imaging technique and MIP-TF mice;2)to explore the roles of ?-arrestin2(?arr2)and NOS1 AP,adapter proteins,in regulation of ? cell mass and its potential mechanisms.Methods Diabetic mice were produced by stretozotocin(STZ)(200mg/kg)injection intraperitoneally.Beta-cell proliferation and apoptosis were assayed by fluorescence-activated cell sorter analysis.qRT-PCR and immunoblotting were conducted for gene and protein expression.Results 1)In MIP-TF mice,the fluorescence intensity reflecting the pancreatic ?-cell mass was statistically higher after glucose stimulation than that before glucose stimulation(P<0.05);the bioluminescence intensity was higher in HFD-fed MIP-TF mice than that in the chow-fed control mice(P<0.05);the fluorescence intensity disappeared completely after STZ injection.2)Overexpression of ?arr2 amplified beta-cell proliferation with concomitant increase in cyclinD2 expression and decrease in p21 expression;the knockdown of ?arr2 significantly increased ? cell apoptosis induced by high glucose and free fatty acids(FFA);Conversely,overexpression of ?arr2 protected beta-cells from glucose-and FFA-induced cell death through JNK-activation inhibition.3)Overexpression of NOS1 AP abolished high concentration of glucose,palmitate or thapsigargin induced the endoplasmic reticulum stress in INS-1(832/13)cells(all P <0.05).Conclusion The platform based on MIP-TF mice for in vivo pancreaticbeta-cells mass detection technology has high sensitivity and specificity,and can be used as an animal model tool for detecting beta-cell mass dynamically in diabetic researches.Both ?arr2 and NOS1 AP play roles in regulation of pancreatic beta-cell mass,which implicates these proteins as therapeutic targets for treatment of diabetes.