Here, we used the global Prlr null mice on a C57BL/6 background, a strain highly sensitive to the diabetogenic drug STZ (21, 22), and show that, when challenged with STZ, these animals are more susceptible to developing hyperglycemia and have a more severe hyperglycemic phenotype as revealed by higher blood glucose levels, glucose intolerance, islet loss, reduced β-cell number and survival, and increased pancreatic inflammation. This evidence concerns the gene PRLR and Glucose intolerance.