Secretory stimuli distinctly regulate insulin secretory granule maturation through structural remodeling
Year: 2025
Type: article
Abstract: Insulin secretory granule (ISG) maturation is a crucial aspect of insulin secretion and glucose homeostasis. The regulation of this maturation remains poorly understood, especially how secretory stimuli affect ISG maturity and subcellular localization. In this study, we used soft X-tomography (SXT) to quantitatively map ISG morphology, density, and location in single INS-1E and mouse pancreatic β-cells under the effect of various secretory stimuli. We found that the activation of glucokinase (GK), gastric inhibitory polypeptide receptor (GIPR), glucagon-like peptide-1 receptor (GLP-1R), and G-protein coupled receptor 40 (GPR40) promote ISG maturation. Each stimulus induces unique structural remodeling in ISGs, by altering size and density, depending on the specific signaling cascades activated. These distinct ISG subpopulations mobilize and redistribute in the cell altering overall cellular structural organization. Our results provide insight into how current diabetes and obesity therapies impact ISG maturation and may inform the development of future treatments that target maturation specifically.
Source: Structure
Authors: Aneesh Deshmukh, Kevin Chang, Janielle Cuala, Maria J. Hernandez Campos, Shayan Mahmood, Riva Verma, Senta Georgia, Valentina Loconte, Kate L. White
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $9,350
Awards: G1286236842, G1337544421, G223002938, A generalizable platform to identify cellular mechanisms that enhance secretory efficiency, G2539837713, G3083819904, G382641700, G42916606, Biological Soft X-ray Tomography at the Advanced Light Source, G6576295377, G6669596460, G7787287669, Beta cell dysfunction as an acute and a post acute sequelae of COVID19, Mentoring Emerging Researchers at CHLA (MERCH-LA), G969889393
OpenAlex ID: W4413683713