WFRF:(MacDonald T. J.)
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A pancreatic islet-specific microRNA regulates insulin secretion
- Poy, MN (author)
-
- Eliasson, Lena (author)
- Lund University,Lunds universitet,Diabetes - öcellsexocytos,Forskargrupper vid Lunds universitet,Diabetes - Islet Cell Exocytosis,Lund University Research Groups
- Krutzfeldt, J (author)
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- Kuwajima, S (author)
- Pfeffer, B (author)
- Tuschl, T (author)
- Rajewsky, N (author)
- Stoffel, M (author)
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- (creator_code:org_t)
- Springer Science and Business Media LLC, 2004
- 2004
- English.
- In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 432:7014, s. 226-230
- Journal article (peer-reviewed)
Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
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- Poy, MN
- Eliasson, Lena
- Krutzfeldt, J
- Kuwajima, S
- Ma, Xiaosong
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- Pfeffer, B
- Tuschl, T
- Rajewsky, N
- Rorsman, Patrik
- Stoffel, M
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- MEDICAL AND HEALTH SCIENCES
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- Lund University
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