A pancreatic islet-specific microRNA regulates insulin secretion
(2004) In Nature 432(7014). p.226-230- Abstract
- MicroRNAs (miRNAs) constitute a growing class of non-coding RNAs that are thought to regulate gene expression by translational repression(1). Several miRNAs in animals exhibit tissue-specific or developmental-stage-specific expression, indicating that they could play important roles in many biological processes(2-4). 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... (More)
- MicroRNAs (miRNAs) constitute a growing class of non-coding RNAs that are thought to regulate gene expression by translational repression(1). Several miRNAs in animals exhibit tissue-specific or developmental-stage-specific expression, indicating that they could play important roles in many biological processes(2-4). 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/263672
- author
- organization
- publishing date
- 2004
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Nature
- volume
- 432
- issue
- 7014
- pages
- 226 - 230
- publisher
- Nature Publishing Group
- external identifiers
-
- wos:000225020200048
- pmid:15538371
- scopus:9144270691
- pmid:15538371
- ISSN
- 0028-0836
- DOI
- 10.1038/nature03076
- language
- English
- LU publication?
- yes
- id
- 346ccc2b-37a2-440d-825a-9184ea38ac21 (old id 263672)
- date added to LUP
- 2016-04-01 12:26:39
- date last changed
- 2022-04-21 07:26:59
@article{346ccc2b-37a2-440d-825a-9184ea38ac21, abstract = {{MicroRNAs (miRNAs) constitute a growing class of non-coding RNAs that are thought to regulate gene expression by translational repression(1). Several miRNAs in animals exhibit tissue-specific or developmental-stage-specific expression, indicating that they could play important roles in many biological processes(2-4). 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.}}, author = {{Poy, MN and Eliasson, Lena and Krutzfeldt, J and Kuwajima, S and Ma, Xiaosong and MacDonald, Patrick and Pfeffer, B and Tuschl, T and Rajewsky, N and Rorsman, Patrik and Stoffel, M}}, issn = {{0028-0836}}, language = {{eng}}, number = {{7014}}, pages = {{226--230}}, publisher = {{Nature Publishing Group}}, series = {{Nature}}, title = {{A pancreatic islet-specific microRNA regulates insulin secretion}}, url = {{http://dx.doi.org/10.1038/nature03076}}, doi = {{10.1038/nature03076}}, volume = {{432}}, year = {{2004}}, }