Unknown

Dataset Information

0

Beta cell secretion of miR-375 to HDL is inversely associated with insulin secretion.


ABSTRACT: Extracellular microRNAs (miRNAs) are a new class of biomarkers for cellular phenotypes and disease, and are bioactive signals within intercellular communication networks. Previously, we reported that miRNAs are secreted from macrophage to high-density lipoproteins (HDL) and delivered to recipient cells to regulate gene expression. Despite the potential importance of HDL-miRNAs, regulation of HDL-miRNA export from cells has not been fully studied. Here, we report that pancreatic islets and beta cells abundantly export miR-375-3p to HDL and this process is inhibited by cellular mechanisms that promote insulin secretion. Small RNA sequencing and PCR approaches were used to quantify beta cell miRNA export to HDL. Strikingly, high glucose conditions were found to inhibit HDL-miR-375-3p export, which was dependent on extracellular calcium. Likewise, stimulation of cAMP was found to repress HDL-miR-375-3p export. Furthermore, we found that beta cell ATP-sensitive potassium channel (KATP) channels are required for HDL-miRNA export as chemical inhibition (tolbutamide) and global genetic knockout (Abcc8-/-) approaches inhibited HDL-miR-375-3p export. This process is not likely associated with cholesterol flux, as gain-of-function and loss-of-function studies for cholesterol transporters failed to alter HDL-miR-375-3p export. In conclusion, results support that pancreatic beta cells export miR-375-3p to HDL and this process is inversely regulated to insulin secretion.

SUBMITTER: Sedgeman LR 

PROVIDER: S-EPMC6405899 | biostudies-other | 2019 Mar

REPOSITORIES: biostudies-other

altmetric image

Publications

Beta cell secretion of miR-375 to HDL is inversely associated with insulin secretion.

Sedgeman Leslie R LR   Beysen Carine C   Ramirez Solano Marisol A MA   Michell Danielle L DL   Sheng Quanhu Q   Zhao Shilin S   Turner Scott S   Linton MacRae F MF   Vickers Kasey C KC  

Scientific reports 20190307 1


Extracellular microRNAs (miRNAs) are a new class of biomarkers for cellular phenotypes and disease, and are bioactive signals within intercellular communication networks. Previously, we reported that miRNAs are secreted from macrophage to high-density lipoproteins (HDL) and delivered to recipient cells to regulate gene expression. Despite the potential importance of HDL-miRNAs, regulation of HDL-miRNA export from cells has not been fully studied. Here, we report that pancreatic islets and beta c  ...[more]

Similar Datasets

| S-EPMC2656556 | biostudies-literature
2019-06-17 | PXD012610 | Pride
| S-EPMC9951314 | biostudies-literature
| S-EPMC8493072 | biostudies-literature
| S-EPMC2793253 | biostudies-literature
| S-EPMC5095347 | biostudies-literature
| S-EPMC5780059 | biostudies-literature
| S-EPMC7506835 | biostudies-literature
2015-06-30 | E-GEOD-48195 | biostudies-arrayexpress
| S-EPMC9391603 | biostudies-literature