Abstract
MicroRNAs (miRNAs) constitute a growing class of non-coding RNAs that are thought to regulate gene expression by translational repression1. Several miRNAs in animals exhibit tissue-specific or developmental-stage- specific expression, indicating that they could play important roles in many biological processes2-4. 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.
Original language | English (US) |
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Pages (from-to) | 226-230 |
Number of pages | 5 |
Journal | Nature |
Volume | 432 |
Issue number | 7014 |
DOIs | |
State | Published - Nov 11 2004 |
Externally published | Yes |
ASJC Scopus subject areas
- General