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- W4313381799 abstract "Abstract T cells have a major role in the progression of type 1 diabetes (T1D) in human and the non-obese diabetic (NOD) mouse model. Activated T cells have increased insulin receptor (IR) expression on their surface. When T cells with high density of IR from NOD mice were transferred into young irradiated non-diabetic NOD mice, recipient mice developed insulitis and diabetes. Irradiated non-diabetic NOD mice that received T cells with low to negative density of IR had neither insulitis nor diabetes. In order to understand the effect of IR expressing T cells in T1D development, our lab has developed a novel transgenic mouse model, C57BL/6-CD3FLAGmIR/mfm, genetically modified to express FLAG tagged mouse insulin receptor (mIR) on T cells. It was observed that FLAG-mIR expressing T cells can chemotax to the islet leading to insulitis. However, C57BL/6-CD3FLAGmIR/mfm mice were not hyperglycemic at any age. Metabolic studies were performed to evaluate if FLAG-mIR expressing T cell infiltration in the transgenic mice has effect on beta cell functionality. Impaired in vitro islet insulin secretion on treatment with non-glucose beta cells secretagogue and abnormal glucose tolerance in the transgenic mice resemble the pathological changes during prediabetes in human and NOD mice. Islet and Metabolic changes were also found in immunocompromised RAG mice that received transgenic mice splenocytes confirming that the transgenic phenotype can be passaged to immunocompromised RAG mice in a short time frame. This study provides a new perspective to understand the pathology of T1D and design a novel therapeutic approach targeting IR overexpressing T cells." @default.
- W4313381799 created "2023-01-06" @default.
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- W4313381799 date "2018-05-01" @default.
- W4313381799 modified "2023-09-30" @default.
- W4313381799 title "Effect of insulin receptor expressing T cell infiltration in islets on beta cell functionality" @default.
- W4313381799 doi "https://doi.org/10.4049/jimmunol.200.supp.102.6" @default.
- W4313381799 hasPublicationYear "2018" @default.
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