Summarily, our results indicate that secretion of glucagon is impaired in islets lacking Vhlh and suggest a likely mechanism for the hypoglycemia in Pdx-1-Creearly;VhlhLoxP/LoxP, Ngn3-Cre;VhlhLoxP/LoxP and Rfx6;VhlhLoxP/LoxP mice. This evidence concerns the gene NEUROG3 and Hypoglycemia.