Glucose-induced regulation of COX-2 expression in human islets of Langerhans.
Cyclo-oxygenase (COX), the enzyme responsible for conversion of arachidonic acid to prostanoids, exists as two isoforms. In most tissues, COX-1 is a constitutive enzyme involved in prostaglandin-mediated physiological processes, whereas COX-2 is thought to be induced by inflammatory stimuli. However, it has previously been reported that COX-2 is the dominant isoform in islets and an insulin-secreting beta-cell line under basal conditions. We have investigated the relative abundance of COX-1 and COX-2 mRNAs in MIN6 cells, a mouse insulin-secreting cell line, and in primary mouse and human islets. We found that COX-2 was the dominant isoform in MIN6 cells, but that COX-1 mRNA was more abundant than that of COX-2 in freshly isolated mouse islets. Furthermore, COX-2 expression was induced by maintenance of mouse islets in culture, and experiments with human islets indicated that exposure of the islets to hyperglycemic conditions was sufficient to upregulate COX-2 mRNA levels. Given that hyperglycemia has been reported to increase human beta-cell production of interleukin-1beta and that this cytokine can induce COX-2 expression, our observations of glucose-induced induction of COX-2 in human islets suggest that this is one route through which hyperglycemia may contribute to beta-cell dysfunction.
Persaud
Shanta J
SJ
Centre for Reproduction, Endocrinology and Diabetes, King's College London, London, UK. shanta.persaud@kcl.ac.uk
Burns
Chris J
CJ
Belin
Véronique D
VD
Jones
Peter M
PM
D000818:Animals; D001483:Base Sequence; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D017931:DNA Primers; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D007515:Islets of Langerhans / Q000187:drug effects / Q000201:enzymology*; D007527:Isoenzymes / Q000235:genetics*; D008565:Membrane Proteins; D051379:Mice; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects
D017931:DNA Primers; D007527:Isoenzymes; D008565:Membrane Proteins; D012333:RNA, Messenger; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; C496512:Ptgs1 protein, mouse; D005947:Glucose