Pathogenic Role of IκBβ/NFκB signaling in ER Stress Induced β-cell Injury and Death

Intrauterine growth restriction (IUGR) is defined as a failure of the developing fetus to reach its genetic growth potential. IUGR is a well-established independent risk factors for the development of Type II diabetes (T2DM) in adulthood. It is increasingly recognized that T2DM is a chronic inflammatory disease. The transcription factor NFκB has been termed the “master regulator the inflammatory response,” and is a well-studied mediator of innate immunity. Multiple studies have implicated NFκB activity as a central mediator of β-cell apoptosis downstream of ER stress. Our lab is new to the study of diabetes, but the rigor of published research, together with our preliminary data, have led us to develop our overarching hypothesis that IUGR β-cell IκB expression favoring IκBβ/NFκB signaling increases sensitivity to ER stress and contributes to an increased risk of developing T2DM.