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Updated: Jan 28, 2026
Measuring Relative Insulin Secretion using a Co-Secreted Luciferase Surrogate
Published on: June 25, 2019
Beta cell secretion of miR-375 to HDL is inversely associated with insulin secretion
Leslie R Sedgeman1, Carine Beysen2, Marisol A Ramirez Solano3
1Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA.
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.
Insights
Pancreatic beta cells export microRNAs (miRNAs) to high-density lipoproteins (HDL), a process inhibited by insulin secretion mechanisms. This discovery offers new insights into intercellular communication and potential disease biomarkers.
Area of Science:
- Endocrinology
- Molecular Biology
- Biochemistry
Background:
- Extracellular microRNAs (miRNAs) serve as biomarkers for cellular states and diseases.
- MicroRNAs are bioactive molecules involved in intercellular communication, with some secreted via high-density lipoproteins (HDL).
- Regulation of HDL-miRNA export from cells remains poorly understood.
Purpose of the Study:
- To investigate the mechanisms regulating the export of microRNAs from pancreatic beta cells to HDL.
- To explore the relationship between HDL-miRNA export and insulin secretion processes.
Main Methods:
- Small RNA sequencing and quantitative PCR were employed to measure miRNA export to HDL from beta cells.
- Experiments involved manipulating glucose levels, extracellular calcium, cAMP stimulation, and beta cell ATP-sensitive potassium channel (KATP) activity.
- Cholesterol transporter function was modulated to assess its role in miRNA export.
Main Results:
- Pancreatic beta cells abundantly export miR-375-3p to HDL.
- High glucose conditions and cAMP stimulation inhibited HDL-miR-375-3p export, dependent on extracellular calcium.
- Inhibition of beta cell KATP channels (using tolbutamide or genetic knockout) reduced HDL-miR-375-3p export.
- Cholesterol transport did not appear to influence HDL-miR-375-3p export.
Conclusions:
- Pancreatic beta cells export miR-375-3p to HDL.
- The export of miR-375-3p to HDL is inversely regulated by insulin secretion pathways.
- These findings highlight a novel mechanism of intercellular communication involving HDL-miRNAs and pancreatic beta cell function.
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