Regulation of insulin secretion: insights from engineered beta-cell lines.

Abnormalities in insulin secretion are involved in a number of diseases, including type 1 and type 2 diabetes, persistent hyperinsulinemic hypoglycemia of infancy, and insulinoma. Understanding the mechanisms that regulate insulin secretion may allow the development of new therapies for these diseases as well as contribute to our ability to engineer insulin-producing cells for cell replacement therapy of type 1 diabetes. Glucose phosphorylation in beta-cells has been viewed as a key regulatory event in coupling insulin secretion to extracellular glucose concentrations. Work with transformed rodent beta-cell lines as well as recent findings from human progenitor cells induced to differentiate into insulin-producing cells has provided new insights into the role of glucose phosphorylating enzymes in the regulation of insulin secretion.