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

Pinhanços, S.S.; Oliveira, J.T. de; Alves, C.H.; Deus, C.M.; Winter, T.J.J. de; Viana, S.; Reis, F.; Santos, J.; Buitinga, M.; Carlotti, F.; Ferreira, L.; Gotthardt, M.; Jones, J.; Fernandes, H.

doi:doi:10.1016/j.omtn.2025.102498

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 (3 cell dysfunction and/or death. This study aims to identify miRNAs capable of protecting (3 cells from GLTinduced cell death (GICD). A library of 2,080 human miRNA mimics was transfected in (3 cells followed by exposure to GLT. We identified 45 miRNAs capable of protecting (3 cells from GICD and selected miR-642a-3p for further studies. RNA-seq revealed that miR-642a-3p restored the expression of (3 cell identity genes and modulated pathways associated with cell survival and lipid metabolism. Moreover, we showed that transfection of (3 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 642a-3p expression was downregulated in human islets isolated from...Show moreThe 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 (3 cell dysfunction and/or death. This study aims to identify miRNAs capable of protecting (3 cells from GLTinduced cell death (GICD). A library of 2,080 human miRNA mimics was transfected in (3 cells followed by exposure to GLT. We identified 45 miRNAs capable of protecting (3 cells from GICD and selected miR-642a-3p for further studies. RNA-seq revealed that miR-642a-3p restored the expression of (3 cell identity genes and modulated pathways associated with cell survival and lipid metabolism. Moreover, we showed that transfection of (3 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 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 in non-diabetic patients. Overall, we have identified a potential dual role for miR-642a-3p as both a biomarker and a facilitator of (3 cell survival and function, offering a novel theranostic tool for the management of diabetes and/or obesity.Show less

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