A pancreatic islet-specific microRNA regulates insulin secretion. Export

@article{poy:2007, abstract = {MicroRNAs (miRNAs) constitute a growing class of non-coding RNAs that are thought to regulate gene expression by translational repression. Several miRNAs in animals exhibit tissue-specific or developmental-stage-specific expression, indicating that they could play important roles in many biological processes. To study the role of miRNAs in pancreatic endocrine cells we cloned and identified a novel, evolutionarily conserved and islet-specific miRNA (miR-375). Here we show that overexpression of miR-375 suppressed glucose-induced insulin secretion, and conversely, inhibition of endogenous miR-375 function enhanced insulin secretion. The mechanism by which secretion is modified by miR-375 is independent of changes in glucose metabolism or intracellular Ca2+-signalling but correlated with a direct effect on insulin exocytosis. Myotrophin (Mtpn) was predicted to be and validated as a target of miR-375. Inhibition of Mtpn by small interfering (si)RNA mimicked the effects of miR-375 on glucose-stimulated insulin secretion and exocytosis. Thus, miR-375 is a regulator of insulin secretion and may thereby constitute a novel pharmacological target for the treatment of diabetes.}, address = {Laboratory of Metabolic Diseases and Laboratory of RNA Molecular Biology, The Rockefeller University, 1230 York Avenue, New York, New York 10021, USA.}, author = {Poy, M. N. and Eliasson, L. and Krutzfeldt, J. and Kuwajima, S. and Ma, X. and Macdonald, P. E. and Pfeffer, S. and Tuschl, T. and Rajewsky, N. and Rorsman, P. and Stoffel, M.}, citeulike-article-id = {172400}, citeulike-linkout-0 = {http://dx.doi.org/10.1038/nature03076}, citeulike-linkout-1 = {http://dx.doi.org/10.1038/nature03076}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/15538371}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=15538371}, day = {11}, doi = {10.1038/nature03076}, issn = {1476-4687}, journal = {Nature}, keywords = {mirna}, month = {November}, number = {7014}, pages = {226--230}, posted-at = {2009-03-18 20:22:47}, priority = {2}, title = {A pancreatic islet-specific microRNA regulates insulin secretion.}, url = {http://dx.doi.org/10.1038/nature03076}, volume = {432}, year = {2004} }

TY - JOUR ID - poy:2007 L3 - citeulike-article-id:172400 N2 - MicroRNAs (miRNAs) constitute a growing class of non-coding RNAs that are thought to regulate gene expression by translational repression. Several miRNAs in animals exhibit tissue-specific or developmental-stage-specific expression, indicating that they could play important roles in many biological processes. To study the role of miRNAs in pancreatic endocrine cells we cloned and identified a novel, evolutionarily conserved and islet-specific miRNA (miR-375). Here we show that overexpression of miR-375 suppressed glucose-induced insulin secretion, and conversely, inhibition of endogenous miR-375 function enhanced insulin secretion. The mechanism by which secretion is modified by miR-375 is independent of changes in glucose metabolism or intracellular Ca2+-signalling but correlated with a direct effect on insulin exocytosis. Myotrophin (Mtpn) was predicted to be and validated as a target of miR-375. Inhibition of Mtpn by small interfering (si)RNA mimicked the effects of miR-375 on glucose-stimulated insulin secretion and exocytosis. Thus, miR-375 is a regulator of insulin secretion and may thereby constitute a novel pharmacological target for the treatment of diabetes. IS - 7014 JF - Nature SN - 1476-4687 AD - Laboratory of Metabolic Diseases and Laboratory of RNA Molecular Biology, The Rockefeller University, 1230 York Avenue, New York, New York 10021, USA. EP - 230 TI - A pancreatic islet-specific microRNA regulates insulin secretion. VL - 432 SP - 226 KW - mirna AU - Poy, MN AU - Eliasson, L AU - Krutzfeldt, J AU - Kuwajima, S AU - Ma, X AU - Macdonald, PE AU - Pfeffer, S AU - Tuschl, T AU - Rajewsky, N AU - Rorsman, P AU - Stoffel, M PY - 2004/11/11/ UR - http://dx.doi.org/10.1038/nature03076 ER -