Diabetes Enhances the Proliferation of Adult Pancreatic Multipotent Progenitor Cells and Biases Their Differentiation to More Beta-Cell Production

Endogenous pancreatic multipotent progenitors (PMPs) are ideal candidates for regenerative approaches to compensate for b-cell loss since their b-cell–producing capacities as well as strategic location would eliminate unnecessary invasive manipulations. However, little is known about the status and potentials of PMPs under diabetic conditions. Here we show that b-cell metabolic stress and hyperglycemia enhance the proliferation capacities of adult PMP cells and bias their production of progeny toward b-cells in mouse and human. These effects are dynamic and correlate with functional b-cell regeneration when conditions allow. Overall design: Insulin-positive Glut2-low cell population of adult pancreatic tissue is enriched for PMP cells. Streptozocin (STZ) can enter beta-cells via Glut2 , induce cell death and consequently diabetes. Insulin-positive cells from two groups (STZ-injected experiment and vehicle-injected control, n=3/group) of MIP-GFP transgenic male mice were sorted to Glut2-low (Glut2L) and Glut2-high (Glut2H) by FACS. Total RNA from these samples were extracted for transcriptome analysis.