miRNA-642a-3p protects β cells from glucolipotoxicity

The incidence of type 2 diabetes mellitus (T2DM) is tightly linked to obesity. High levels of circulating glucose and saturated free fatty acids (FFAs), known as glucolipotoxicity (GLT), is implicated in β cell dysfunction and/or death. This study aims to identify miRNAs capable of protecting β cells from GLT-induced cell death (GICD). A library of 2,080 human miRNA mimics was transfected in β cells followed by exposure to GLT. We identified 45 miRNAs capable of protecting β cells from GICD and selected miR-642a-3p for further studies. RNA-seq revealed that miR-642a-3p restored the expression of β cell identity genes and modulated pathways associated with cell survival and lipid metabolism. Moreover, we showed that transfection of β cells with miR-642a-3p protected them from GLT-induced changes in insulin secretion. Compared with the control, hypercaloric-fed mice showed a trend toward decreased expression of GLT-protective miRNAs. Notably, we demonstrated that miR-642a-3p expression was downregulated in human islets isolated from T2DM patients compared with non-diabetic controls. Importantly, in obese patients, the expression of GLT-protective miRNAs in plasma-derived extracellular vesicles was increased in non-diabetic patients. Overall, we have identified a potential dual role for miR-642a-3p as both a biomarker and a facilitator of β cell survival and function, offering a novel theranostic tool for the management of diabetes and/or obesity.

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Publication Details

Journal
Molecular Therapy — Nucleic Acids
Published
2025-03-26
DOI
https://doi.org/10.1016/j.omtn.2025.102498
Citations
1
Primary Topic
Pancreatic function and diabetes
Type
article
Field-Weighted Citation Impact
2.01

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article

miRNA-642a-3p protects β cells from glucolipotoxicity

C. Henrique Alves, Françoise Carlotti, Cláudia M. Deus, Twan J. J. de Winter et al.
1 citations
Molecular Therapy — Nucleic Acids
Pancreatic function and diabetes
2.01
article

miRNA-642a-3p protects β cells from glucolipotoxicity

C. Henrique Alves, Françoise Carlotti, Cláudia M. Deus, Twan J. J. de Winter, Flávio Reis, Martin Gotthardt, Jorge Francisco Kuhn dos Santos, John G. Jones, Sofia Viana, Joana Oliveira, Sandra S. Pinhanços, Mijke Buitinga, Lino Ferreira, Hugo Fernandes
article en
1 citations

Abstract

The incidence of type 2 diabetes mellitus (T2DM) is tightly linked to obesity. High levels of circulating glucose and saturated free fatty acids (FFAs), known as glucolipotoxicity (GLT), is implicated in β cell dysfunction and/or death. This study aims to identify miRNAs capable of protecting β cells from GLT-induced cell death (GICD). A library of 2,080 human miRNA mimics was transfected in β cells followed by exposure to GLT. We identified 45 miRNAs capable of protecting β cells from GICD and selected miR-642a-3p for further studies. RNA-seq revealed that miR-642a-3p restored the expression of β cell identity genes and modulated pathways associated with cell survival and lipid metabolism. Moreover, we showed that transfection of β cells with miR-642a-3p protected them from GLT-induced changes in insulin secretion. Compared with the control, hypercaloric-fed mice showed a trend toward decreased expression of GLT-protective miRNAs. Notably, we demonstrated that miR-642a-3p expression was downregulated in human islets isolated from T2DM patients compared with non-diabetic controls. Importantly, in obese patients, the expression of GLT-protective miRNAs in plasma-derived extracellular vesicles was increased in non-diabetic patients. Overall, we have identified a potential dual role for miR-642a-3p as both a biomarker and a facilitator of β cell survival and function, offering a novel theranostic tool for the management of diabetes and/or obesity.

Molecular Therapy — Nucleic AcidsVol. 36(2)
Radboud University Nijmegen (NL), Universidade do Porto (PT), Leiden University Medical Center (NL), Maastricht University Medical Centre (NL), Radboud University Medical Center (NL), Polytechnic Institute of Coimbra (PT), Maastricht University (NL), Association for Innovation and Biomedical Research on Light and Image (PT), Centro Hospitalar do Porto (PT), University of Coimbra (PT)
Sociedade Portuguesa De Diabetologia, European Commission, ZonMw, Ministério da Ciência, Tecnologia e Ensino Superior, HORIZON EUROPE Framework Programme, Fundação para a Ciência e a Tecnologia
Zero hunger
Openalex Percentile: Top 18%
Pancreatic function and diabetes
2.01
DOIOpen Access PDFOpenAlex
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