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

摘要

Pancreatic β cells respond to changes in blood glucose by secreting insulin and increasing insulin synthesis. To identify genes used in these responses, we have carried out expression profiling of β cells exposed to high (25 mM) or low (5.5 mM) glucose by using oligonu- cleotide microarrays. Functional clustering of genes that averaged a 2.2-fold or greater change revealed large groups of secretory path- way components, enzymes of intermediary metabolism, cell-signal- ing components, and transcription factors. Many secretory pathway genes were up-regulated in high glucose, including seven members of the endoplasmic reticulum (ER) translocon. In agreement with array analysis, protein levels of translocon components were increased by high glucose. Most dramatically. the α subunit of the signal recogni- tion particle receptor was increased over 20-fold. These data indicate that the translocon and ribosome docking are major regulatory targets of glucose in the β cell. Analysis of genes encoding enzymes of intermediary metabolism indicated that low glucose brought about greater utilization of amino acids as an energy source. This conclusion was supported by observations of increased urea produc- tion under low-glucose conditions. The above results demonstrate genome-wide integration of β-cell functions at the level of transcript abundance and validate the efficacy of expression profiling in iden- tifying genes involved in the β-cell glucose response.