A pancreatic islet-specific microRNA regulates insulin secretion

MN Poy, L Eliasson, J Krutzfeldt, S Kuwajima, X Ma… - Nature, 2004 - nature.com
Nature, 2004nature.com
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 …
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.
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