Year: 2023
Type: article
Abstract: Insulin secretion is a tightly regulated process that is vital for maintaining blood glucose homeostasis. Although the molecular components of insulin granule trafficking and secretion are well established, how they are regulated to rapidly fine-tune secretion in response to changing environmental conditions is not well characterized. Recent studies have determined that dysregulation of RNA-binding proteins (RBPs) and aberrant mRNA splicing occurs at the onset of diabetes. We demonstrate that the RBP, RBFOX2, is a critical regulator of insulin secretion through the alternative splicing of genes required for insulin granule docking and exocytosis. Conditional mutation of Rbfox2 in the mouse pancreas results in decreased insulin secretion and impaired blood glucose homeostasis. Consistent with defects in secretion, we observe reduced insulin granule docking and corresponding splicing defects in the SNARE complex components. These findings identify an additional mechanism for modulating insulin secretion in both healthy and dysfunctional pancreatic β cells.
Source: Nature Communications
Authors: Nicole D. Moss, Kristen L. Wells, Alexandra Theis, Yong-Kyung Kim, Aliya F. Spigelman, Xiong Liu, Patrick E. MacDonald, Lori Sussel
Institutions: University of Colorado Anschutz, University of Alberta
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $6,290
Funders: U.S. Department of Health and Human Services, Diabetes Research Connection, Government of Canada, National Institutes of Health, Anschutz Medical Campus, University of Colorado, Canadian Institutes of Health Research, Natural Sciences and Engineering Research Council of Canada, National Institute of Diabetes and Digestive and Kidney Diseases
Awards: G1104028309, G1407765081, G2117831693, G2449682216, Groucho co-repressors in the regulation of pancreatic islet development, G5489155565, G6006929006, O-Tesla magnet: A simulated fMRI facility, G6874227037, G7232004784, PTPN2 mutations affect islet beta cell susceptibility in T1D, G9000126259, University of Colorado Anschutz Medical Campus DRC, Regulation of pancreatic islet cell fate, Alternative RNA splicing events contribute to the onset of islet dysfunction in T1D, RNA Regulation in the Pancreatic Beta Cell
OpenAlex ID: W4388998622