RNA binding protein HuD regulates the biosynthesis of glucagon-like peptide 1 in intestinal L-cells
Sukyoung Han1,2, Myeongwoo Jung1,3, Seungyeon Ryu1,2
1Department of Biochemistry, College of Medicine, The Catholic University of Korea, Seoul, 06591, South Korea.
Abstract:
We investigated HuD (ELAVL4), a neuronal RNA-binding protein with emerging endocrine functions, as a regulator of GLP-1 biogenesis in intestinal L-cells. Using absolute qPCR and immunofluorescence, we found that HuD was significantly expressed in the GLUTag cells derived from mice intestinal L-cell line and was co-localized with GLP-1-positive cells in the small intestine of mice. RNA interference-mediated HuD knockdown reduced both GLP-1 immunoreactivity and levels. Mechanistically, RNA immunoprecipitation and biotinylated 3'UTR pull-down demonstrated that HuD binds to the mRNAs of the Gcg and Pcsk1 (PC1/3) genes. The levels of the proglucagon (∼17 kDa) and PC1/3 proteins decreased without significant changes in their mRNAs, suggesting post-transcriptional control. Metabolic stress converged on this module: palmitate decreased proglucagon/PC1/3 in GLUTag cells, and a high-fat diet reduced GLP-1 and PC1/3 signals in the mouse intestine. Interestingly, zinc sulfate partially restored proglucagon and PC1/3 levels following palmitate treatment. These findings reveal a HuD-Gcg/Pcsk1 axis is crucial for GLP-1 biogenesis and which is susceptible to lipotoxic stress.
More Related Videos
07:00Mechanisms Underlying Gut Hormone Secretion Using the Isolated Perfused Rat Small Intestine
Published on: February 26, 2019
07:05Important Endpoints and Proliferative Markers to Assess Small Intestinal Injury and Adaptation using a Mouse Model of Chemotherapy-Induced Mucositis
Published on: May 12, 2019
Related Concept Videos
Glucagon-like Receptor Agonists
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by...
Hormones Regulating Blood Glucose
In addition to accelerating glucose uptake and utilization, insulin has...
Cell Specific Gene Expression
Insulin: The Receptor and Signaling Pathways
Glucose Homeostasis: Pancreatic Islets and Insulin Secretion
Insulin and C-peptide are...
Insulin Secretory Vesicles
