Expression of the insulin gene: regulation by glucose, hydrocortisone and growth hormone in mouse pancreatic islets in organ culture

Abstract

Isolated pancreatic islets from mouse were maintained in organ culture at either 3.3 mM glucose or 20 mM glucose to study the effect of glucose on the level of preproinsulin mRNA. In islets cultured at 20 mM glucose for up to 7 days, the level of preproinsulin mRNA remained constant, but in islets kept at 3.3 mM glucose the preproinsulin mRNA level decreased within 24 h to one tenth of the level in islets maintained at 20 mM glucose. The level of preproinsulin mRNA could, however, be completely restored by subsequent incubation at 20 mM glucose for 3 days. These results suggest that glucose has a direct effect on the level of preproinsulin mRNA in pancreatic islets. The biosynthesis of proinsulin was correlated to the variation in the level of the preproinsulin mRNA, suggesting that the rate of biosynthesis of proinsulin is limited by the level of the preproinsulin mRNA. Initial experiments with hydrocortisone and human growth hormone, both known to enhance insulin release from islets in organ culture, showed that the level of preproinsulin mRNA was increased in islets cultured in the presence of these hormones.