Expression profiling of pancreatic cells: glucose regulation of secretory and metabolic pathway genes

The -cell of the pancreatic islets of Langerhans is aprimary component in vertebrate glucose homeo-stasis. -Cells sense glucose levels directly via itsmetabolism and respond by secretion of insulin from storage granules formed in the regulated secretory pathway. This stimulus-secretion coupling takes place on the order of seconds/minutes and entails ATP production from glucose metabolism. -Cells also respond to glucose in the longer term (minutes/hours) by increasing preproinsulin biosynthesis at the endoplasmic reticulum (ER) membrane (1,2). Derangement of this process leads to reduced insulin production and is a factor in the development of diabetes (3). Type 2 diabetes is characterized by reduced -cell insulin stores, suggesting that the diabetic -cell is unable to syn-thesize a sufficient quantity of insulin (4). Insulin produc-tion is primarily regulated by glucose at the level of pre-proinsulin mRNA translation (1,5), whereas regulation of transcription of the preproinsulin gene can provide longer