Noninvasive Monitoring of Changes in Pancreatic Beta-cell Mass by Bioluminescent Imaging in MIP-lucTransgenic Mice

Abstract

We have generated a transgenic mouse model (MIP- LUC) that allows real-time imaging of insulin-secreting pancreatic beta cells in living mice. The beta cells of MIP- LUC transgenic mice emit a light signal that can be visualized externally by bioluminescent imaging using specialized equipment. In order to determine whether the intensity of the bioluminescent signal accurately reflects changes in beta-cell mass rather than simply transcriptional modulation of the mouse insulin I promoter-luciferase transgene, we examined the correlation between the bioluminescent signal and the beta-cell mass in MIP- LUC mice fed a regular or high-fat Western diet. Male MIP- LUC mice were fed a standard rodent diet (5% of calories from fat) or a high-fat Western diet (42% from fat) beginning at 4 weeks of age. The bioluminescent signal and beta-cell mass were measured after 6 and 10 weeks on each diet. The body weight, beta-cell mass, and bioluminescent signal increased with age and increased further in mice fed a high-fat diet. There was a statistically significant correlation between beta-cell mass and bioluminescent signal (r (2)=0.660, p=0.00137). Thus, in vivo bioluminescent imaging can be used to noninvasively monitor changes in beta-cell mass in living MIP- LUC mice, and it complements other approaches for monitoring beta-cell mass in states of insulin resistance, obesity, and diabetes.