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MicroRNA-7a regulates pancreatic β cell function
Open accessAbstract
Dysfunctional microRNA (miRNA) networks contribute to inappropriate responses following pathological stress and are the underlying cause of several disease conditions. In pancreatic β cells, miRNAs have been largely unstudied and little is known about how specific miRNAs regulate glucose-stimulated insulin secretion (GSIS) or impact the adaptation of β cell function to metabolic stress. In this study, we determined that miR-7 is a negative regulator of GSIS in β cells. Using Mir7a2 deficient mice, we revealed that miR-7a2 regulates β cell function by directly regulating genes that control late stages of insulin granule fusion with the plasma membrane and ternary SNARE complex activity. Transgenic mice overexpressing miR-7a in β cells developed diabetes due to impaired insulin secretion and β cell dedifferentiation. Interestingly, perturbation of miR-7a expression in β cells did not affect proliferation and apoptosis, indicating that miR-7 is dispensable for the maintenance of endocrine β cell mass. Furthermore, we found that miR-7a levels are decreased in obese/diabetic mouse models and human islets from obese and moderately diabetic individuals with compensated β cell function. Our results reveal an interconnecting miR-7 genomic circuit that regulates insulin granule exocytosis in pancreatic β cells and support a role for miR-7 in the adaptation of pancreatic β cell function in obesity and type 2 diabetes.
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“GIIS is enhanced in mir-7a knockout mice (371), despite there being no obvious effect on [Ca2+]i or the number of docked granules.”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [371]
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“MiR-7 is the 2nd most abundant miR in human β-cells.”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [371]
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Metadata
- Authors
- Latreille, M., Hausser, J., Stützer, I., Zhang, Q., Hastoy, B., Gargani, S., Kerr-Conte, J., Pattou, F., Zavolan, M., Esguerra, J. L. S., Eliasson, L., Rülicke, T., Rorsman, P., & Stoffel, M.
- Affiliations
- Inserm (FR)
- University of Basel (CH)
- Churchill Hospital (GB)
- Université de Lille (FR)
- University of Veterinary Medicine Vienna (AT)
- Corresponding author
- Stoffel, Markus
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 2014-05-01
- Volume
- 124
- Issue
- 6
- Pages
- 2722-2735
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC4038573
- OpenAlex
- W2129743050
- Cited by
- 281
- References
- 63
- Citations by year
- 2026: 5 · 2025: 12 · 2024: 17 · 2023: 20 · 2022: 26 · 2021: 27 · 2020: 26 · 2019: 30 · 2018: 32 · 2017: 24 · 2016: 15 · 2015: 35 · 2014: 11
- FWCI
- 28.11
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Clinical Investigation (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion, other-oa)
- Funders
- National Science Foundation
- Fondation de l'Avenir pour la Recherche Médicale Appliquée
- Wellcome Trust (095531/Z/11/Z, 095531)
- European Genomic Institute for Diabetes (ANR-10-LABX-46)
- European Foundation for the Study of Diabetes
- Agence Nationale de la Recherche (ANR‐10‐LABX‐46, 10-LABX-46, ANR-10)
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (127307)
- Eidgenössische Technische Hochschule Zürich
- Crafoordska Stiftelsen
- Knut och Alice Wallenbergs Stiftelse
- Vetenskapsrådet
- Veterinärmedizinische Universität Wien
- Region Skåne
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Keywords
- microRNA, pancreatic beta cells, glucose-stimulated insulin secretion, insulin granule exocytosis, SNARE complex, beta-cell dedifferentiation, type 2 diabetes, obesity, islets, beta-cell function
- MeSH terms
- Insulin Secretion, Animals, Diabetes Mellitus, Exocytosis, Humans, Insulin, Mice, Inbred C57BL, Mice, Obese, Mice, Transgenic, Obesity, Mice, Knockout, MicroRNAs, Insulin-Secreting Cells, SNARE Proteins, Mice, Cell Dedifferentiation
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