A JournAl of the AmericAn DiAbetes AssociAtion

Immunology/TransplantationExpression of phospho-p38 in exendin-4 treated CD4+ T lymphocytes andmonocytesCell type Group Medium(MFI/104 leucocytes)Th cellsMonocytesADA-Funded ResearchControlT1DMT2DMControlT1DMT2DM2.97 (2.4-4.1)5.5 (3.4-7.5)6.65 (5.3-7.1)14.8 (13.5-24.2)25.3 (15.9-25.8)32.9 (25.7-64.9)Medium(MFI/104 leucocytes)2.7 (2.3-3.9)4.4 (3.3-4.9)*4.4 (3.9-6.1)*14.6 (13.4-23.1)20.7 (15.8-22.1)*26.2 (20.7-53.2)*76-LBThe Role of TRIF in the Development of Type 1 Diabetes (T1D) inNonobese Diabetic MiceCHEN CHAO, MONIKA MAJEWSKA, YIPENG WANG, YUFEI XIANG, NINGWENTAI, JIAN PENG, ZHIGUANG ZHOU, LI WEN, New Haven, CT, Changsha, ChinaTIR-domain-containing adapter-inducing interferon-β (TRIF) is an adaptorfor activation of some Toll Like Receptors (TLRs). It mediates one of two TLRassociatedsignaling cascades, where TRIF mediates a more delayed cascadeand the other is dependent upon the MyD88 adaptor. In addition to thecommon MyD88-dependent pathway, TLR3 & 4 utilize a MyD88-independentsignaling pathway that leads to the activation of IRF-3 and induction of IFN-β.To investigate whether TRIF plays a role in T1D development in the NOD mice,we generated TRIF-/-NOD mice. We found that female TRIF-/-NOD mice (n=15)had delayed onset of spontaneous T1D compared to TRIF+/-NOD (n=22) andTRIF+/+NOD mice (n=10) after 8 months observation. Glucose tolerance testshowed that TRIF-/- mice were more insulin sensitive compared to TRIF+/+mice (P