Chronic Exposure to High Glucose Concentrations Increases Proglucagon Messenger Ribonucleic Acid Levels and Glucagon Release from InR1G9 Cells

α cell function is impaired in diabetes. In diabetics, plasma levels of glucagon are high despite persistently elevated glucose levels and may even rise paradoxically in response to a glucose load; high plasma glucagon levels are accompanied by increased proglucagon gene expression. We have investigated the effects of high glucose concentrations on InR1G9 cells, a glucagon-producing cell line. We show here that chronically elevated glucose concentrations increase glucagon release by 2.5- to 4-fold, glucagon cell content by 2.5- to 3-fold, and proglucagon messenger RNA levels by 4- to 8-fold, whereas changes for 24 h have no effect on proglucagon messenger RNA levels. Persistently elevated glucose affects proglucagon gene expression at the level of transcription and insulin is capable of preventing this effect. We conclude that chronically elevated glucose may be an important factor in the α cell dysfunction that occurs in diabetes and thus that glucose may not only affect the β cell but also the α cell.