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 insulin and increasing insulin synthesis. To identify genes used in these responses, we have carried out expression profiling of beta cells exposed to high (25 mM) or low (5.5 mM) glucose by using oligonucleotide microarrays. Functional clustering of genes that averaged a 2.2-fold or greater change revealed large groups of secretory pathway components, enzymes of intermediary metabolism, cell-signaling 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 alpha subunit of the signal recognition particle receptor was increased over 20-fold. These data indicate that the translocon and ribosome docking are major regulatory targets of glucose in the beta 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 production under low-glucose conditions. The above results demonstrate genome-wide integration of beta-cell functions at the level of transcript abundance and validate the efficacy of expression profiling in identifying genes involved in the beta-cell glucose response.
Webb
G C
GC
Department of Biochemistry and Molecular Biology, University of Chicago, and Howard Hughes Medical Institute, 5841 South Maryland Avenue, Room N216, Chicago, IL 60637, USA.
Akbar
M S
MS
Zhao
C
C
Steiner
D F
DF
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000235:genetics; D004734:Energy Metabolism / Q000235:genetics; D005089:Exocytosis / Q000235:genetics; D020224:Expressed Sequence Tags; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D005947:Glucose / Q000494:pharmacology*; D007328:Insulin / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D012326:RNA Splicing / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D012636:Secretory Rate / Q000187:drug effects; D015398:Signal Transduction / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics
D018076:DNA, Complementary; D007328:Insulin; D011506:Proteins; D012333:RNA, Messenger; D005947:Glucose