Evaluation of impaired β-cell function in nonobese-diabetic (NOD) mouse model using bioluminescence imaging

Insulin-producing pancreatic beta cells are functionally impaired or destroyed in diabetes mellitus. The onset of type 1 diabetes (T1D) represents the culmination of a prolonged prediabetic phase of immune-mediated beta-cell destruction. To assess the in vivo metabolic status of these cells, we used the ATP-sensitive firefly luciferase bioluminescence imaging approach, as a noninvasive probe to monitor pathological alterations in beta-cell function in the nonobese-diabetic (NOD) mouse model of T1D. Hence, we generated the ToI beta-NOD transgenic mice in which doxycycline-inducible luciferase gene is selectively expressed in beta cells. A sharp reduction in bioluminescence emitted in vivo from beta cells at the early stages, preceded by several weeks of a limited reduction in beta-cell mass. Since this decline could be due to the ongoing inflammatory process occurring in vivo, we exposed control islets to inflammatory cytokines and observed a dramatic decrease in luciferase luminescence, which appears to be due in part to a decrease in protein levels and a drop in intracellular ATP levels. This is the first evidence that selective expression of the luciferase gene represents a sensitive method for noninvasive in vivo monitoring of early beta-cell dysfunction, subtle metabolic changes, such as endogenous ATP levels, indicative of a pathological condition in a tissue at the cellular level.-Sever, D., Eldor, R., Sadoun, G., Amior, L., Dubois, D., Boitard, C., Aflalo, C., Melloul, D. Evaluation of impaired beta-cell function in nonobese-diabetic (NOD) mouse model using bioluminescence imaging. FASEB J. 25, 676-684 (2011). www.fasebj.org