A pancreatic islet-specific microRNA regulates insulin secretion
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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MiR-375 is the miRNA with the highest expression in islets and the first to be studied in detail.
“MiR-375 is the miRNA with the highest expression in islets and the first to be studied in detail (517).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [517]
Mouse miR-375 is expressed in pancreatic beta cells and appears to function in the regulation of insulin secretion.
“Although expression of mouse miR-375 in the pituitary has not been ascertained, it is expressed in pancreatic beta cells [45] and appears to function in the regulation of insulin secretion.”
From MicroRNAs show a wide diversity of expression profiles in the developing and mature central nervous system (2007) · cites this paper as [45]
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- Authors
- Poy, M. N., Eliasson, L., Krutzfeldt, J., Kuwajima, S., Ma, X., MacDonald, P. E., Pfeffer, S., Tuschl, T., Rajewsky, N., Rorsman, P., & Stoffel, M.
- Affiliations
- Rockefeller University (US)
- Lund University (SE)
- New York University (US)
- Corresponding author
- Stoffel, Markus
- ORCID
- Venue
- Nature
- Published
- 2004-11
- Volume
- 432
- Issue
- 7014
- Pages
- 226-230
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2135613885
- Cited by
- 2,102
- References
- 4
- Citations by year
- 2026: 31 · 2025: 44 · 2024: 50 · 2023: 61 · 2022: 64 · 2021: 90 · 2020: 79 · 2019: 93 · 2018: 101 · 2017: 122 · 2016: 99 · 2015: 140 · 2014: 144 · 2013: 155 · 2012: 118
- FWCI
- 88.07
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Bern Open Repository and Information System (University of Bern) (submittedVersion)
- MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (submittedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- miR-375, microRNA, insulin secretion, pancreatic islets, insulin exocytosis, myotrophin, glucose-stimulated insulin secretion, diabetes mellitus, protein synthesis inhibition, pancreatic endocrine cells
- MeSH terms
- Insulin Secretion, Animals, Cell Line, Cloning, Molecular, Diabetes Mellitus, Exocytosis, Glucose, Insulin, Islets of Langerhans, Organ Specificity, Potassium Chloride, Substrate Specificity, Tolbutamide, Genetic Therapy, Gene Expression, Calcium Signaling, Gene Silencing, MicroRNAs, Intercellular Signaling Peptides and Proteins, Mice
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