Regulation of the expression of components of the exocytotic machinery of insulin-secreting cells by microRNAs
Open accessAbstract
Fine-tuning of insulin secretion from pancreatic β-cells participates in blood glucose homeostasis. Defects in this process can lead to chronic hyperglycemia and diabetes mellitus. Several proteins controlling insulin exocytosis have been identified, but the mechanisms regulating their expression remain poorly understood. Here, we show that two non-coding microRNAs, miR124a and miR96, modulate the expression of proteins involved in insulin exocytosis and affect secretion of the β-cell line MIN6B1. miR124a increases the levels of SNAP25, Rab3A and synapsin-1A and decreases those of Rab27A and Noc2. Inhibition of Rab27A expression is mediated by direct binding to the 3′-untranslated region of Rab27A mRNA. The effect on the other genes is indirect and linked to changes in mRNA levels. Over-expression of miR124a leads to exaggerated hormone release under basal conditions and a reduction in glucose-induced secretion. miR96 increases mRNA and protein levels of granuphilin, a negative modulator of insulin exocytosis, and decreases the expression of Noc2, resulting in lower capacity of MIN6B1 cells to respond to secretagogues. Our data identify miR124a and miR96 as novel regulators of the expression of proteins playing a critical role in insulin exocytosis and in the release of other hormones and neurotransmitters.
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In mouse insulinoma cells, increased expression of miR-124 stimulated basal insulin secretion and reduced GIIS.
“In mouse insulinoma cells, increased expression of miR-124 stimulated basal insulin secretion and reduced GIIS,”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [401]
The Results (p. 2) report that miR124a overexpression in mouse MIN6B1 cells increased hormone release at low glucose and reduced the response to secretagogues. However, the experiment measured co-released hGH as a proxy for insulin secretion, and the stimulated condition combined glucose with forskolin and IBMX; it did not directly measure glucose-induced insulin secretion alone. (LLM, conf=0.87)
Experimental — accuracy not yet measuredOverexpression of miR-96 inhibits insulin secretion.
“Overexpression of miR-96 also inhibits insulin secretion.”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [401]
The Results (p. 2) report that miR-96 overexpression diminished the secretory response of MIN6B1 cells to glucose and cAMP-raising agents. The unqualified claim is broader than that finding: basal secretion was unaffected, and the experiment measured co-released hGH as a proxy for insulin secretion. (LLM, conf=0.86)
Experimental — accuracy not yet measuredThe effects of miR-124 were mediated by increased expression of SNAP-25 and Rab3a, and reduced expression of Noc-2.
“This was mediated by increased expression of SNAP-25 and Rab3a, and reduced expression of Noc-2 (401).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [401]
The Results (p. 2) report that miR124a increased SNAP25 and Rab3A expression and reduced Noc2 expression in insulin-secreting cells. The paper does not establish that these three changes mediated miR124a’s effects on secretion; the Discussion (p. 5) says the mechanism was not fully defined and finds that increased SNAP25 is unlikely to explain increased basal secretion. (LLM, conf=0.86)
Experimental — accuracy not yet measuredThe effect of miR-96 on insulin secretion may be due to increased expression of granuphilin.
“This effect may be due to increased expression of granuphilin (cf. effect of miR-9) (401).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [401]
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Cites
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- Article in press - uncorrected proof and involved in impaired insulin secretion in diabetic mice. Cell. Metab. 4 , 143-154.
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Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men
Rorsman, P., & Ashcroft, F. M. (2018) · Physiological Reviews · doi:10.1152/physrev.00008.2017 · Cited by 793 · see citing works
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Role of microRNAs in diabetes and its cardiovascular complications
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MicroRNAs in Metabolic Disease
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Chen, H., Lan, H.-Y., Roukos, D. H., & Cho, W. C. (2014) · Journal of Endocrinology · doi:10.1530/joe-13-0544 · Cited by 124 · see citing works
MicroRNA-124 promotes hepatic triglyceride accumulation through targeting tribbles homolog 3
Liu, X., Zhao, J., Liu, Q., Xiong, X., Zhang, Z., Jiao, Y., Li, X., Liu, B., Li, Y., & Lu, Y. (2016) · Scientific Reports · doi:10.1038/srep37170 · Cited by 25 · see citing works
- Authors
- Lovis, P., Gattesco, S., & Regazzi, R.
- Affiliations
- University of Lausanne (CH)
- ORCID
- Regazzi, Romano
- Venue
- bchm
- Publisher
- Walter de Gruyter GmbH
- Published
- 2008-03-01
- Volume
- 389
- Issue
- 3
- Pages
- 305-312
- ISSN
- 1431-6730 (ISSN-L)
- 1437-4315
- OpenAlex
- W2073431065
- Cited by
- 257
- References
- 1
- Citations by year
- 2025: 5 · 2024: 2 · 2023: 10 · 2022: 7 · 2021: 13 · 2020: 12 · 2019: 13 · 2018: 16 · 2017: 23 · 2016: 11 · 2015: 25 · 2014: 27 · 2013: 24 · 2012: 22
- FWCI
- 16.18
- Type
- journal article
- Language
- en
- Open access
- green
- serval.unil.ch
- Licence
- other-oa
- Locations
- Biological Chemistry (publishedVersion)
- PubMed (publishedVersion)
- SERVAL (Université de Lausanne) (publishedVersion, other-oa)
- reroDoc Digital Library (submittedVersion)
- IRIS (submittedVersion)
- Funders
- National Science Foundation
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (113421, 3100A0)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Keywords
- microRNA, insulin exocytosis, pancreatic beta cells, insulin secretion, SNAP-25, Rab3A, Rab27a, 3' untranslated region, diabetes mellitus, blood glucose homeostasis
- MeSH terms
- rab27 GTP-Binding Proteins, Insulin Secretion, Animals, Cell Line, Exocytosis, Colforsin, Glucose, Insulin, Proteins, 1-Methyl-3-isobutylxanthine, Synapsins, rab GTP-Binding Proteins, rab3A GTP-Binding Protein, Vesicular Transport Proteins, MicroRNAs, Intracellular Signaling Peptides and Proteins, Adaptor Proteins, Signal Transducing, Insulin-Secreting Cells, Synaptosomal-Associated Protein 25, Mice
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