A pancreatic islet-specific microRNA regulates insulin secretion.
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...
| Main Authors: | , , , , , , , , , , |
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| Formato: | Journal article |
| Idioma: | English |
| Publicado: |
2004
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| _version_ | 1826265592210915328 |
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| author | Poy, M Eliasson, L Krutzfeldt, J Kuwajima, S Ma, X Macdonald, P Pfeffer, S Tuschl, T Rajewsky, N Rorsman, P Stoffel, M |
| author_facet | Poy, M Eliasson, L Krutzfeldt, J Kuwajima, S Ma, X Macdonald, P Pfeffer, S Tuschl, T Rajewsky, N Rorsman, P Stoffel, M |
| author_sort | Poy, M |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T20:26:05Z |
| format | Journal article |
| id | oxford-uuid:2f70a233-9e5f-4f98-b0f8-dc6037a26ba4 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T20:26:05Z |
| publishDate | 2004 |
| record_format | dspace |
| spelling | oxford-uuid:2f70a233-9e5f-4f98-b0f8-dc6037a26ba42022-03-26T12:55:26ZA pancreatic islet-specific microRNA regulates insulin secretion.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:2f70a233-9e5f-4f98-b0f8-dc6037a26ba4EnglishSymplectic Elements at Oxford2004Poy, MEliasson, LKrutzfeldt, JKuwajima, SMa, XMacdonald, PPfeffer, STuschl, TRajewsky, NRorsman, PStoffel, MMicroRNAs (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. |
| spellingShingle | Poy, M Eliasson, L Krutzfeldt, J Kuwajima, S Ma, X Macdonald, P Pfeffer, S Tuschl, T Rajewsky, N Rorsman, P Stoffel, M A pancreatic islet-specific microRNA regulates insulin secretion. |
| title | A pancreatic islet-specific microRNA regulates insulin secretion. |
| title_full | A pancreatic islet-specific microRNA regulates insulin secretion. |
| title_fullStr | A pancreatic islet-specific microRNA regulates insulin secretion. |
| title_full_unstemmed | A pancreatic islet-specific microRNA regulates insulin secretion. |
| title_short | A pancreatic islet-specific microRNA regulates insulin secretion. |
| title_sort | pancreatic islet specific microrna regulates insulin secretion |
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