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

Pancreatic beta cells respond to changes in blood glucose by secreting insu lin and increasing insulin synthesis. To identify genes used in these respo nses, we have carried out expression profiling of beta cells exposed to hig h (25 mM) or low (5.5 mM) glucose by using oligonucleotide microarrays, Fun ctional clustering of genes that averaged a 2.2-fold or greater change reve aled large groups of secretory pathway components, enzymes of intermediary metabolism, cell-signaling components, and transcription factors, Many secr etory pathway genes were up-regulated in high glucose, including seven memb ers of the endoplasmic reticulum (ER) translocon, In agreement with array a nalysis, protein levels of translocon components were increased by high glu cose, Most dramatically, the or subunit of the signal recognition particle receptor was increased over 20-fold. These data indicate that the transloco n and ribosome docking are major regulatory targets of glucose in the beta cell. Analysis of genes encoding enzymes of intermediary metabolism indicat ed that low glucose brought about greater utilization of amino acids as an energy source, This conclusion was supported by observations of increased u rea production under low-glucose conditions, The above results demonstrate genome-wide integration of beta-cell functions at the level of transcript a bundance and validate the efficacy of expression profiling in identifying g enes involved in the beta-cell glucose response.