DOE OSTI · 3013809
Secretory stimuli distinctly regulate insulin secretory granule maturation through structural remodeling
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-ray 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) promotes 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 the 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.
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Deshmukh, Aneesh [Univ. of Southern California, Los Angeles, CA (United States)], Chang, Kevin [Univ. of Southern California, Los Angeles, CA (United States)], Cuala, Janielle [Univ. of Southern California, Los Angeles, CA (United States)], Hernandez Campos, Maria J. [Monmouth Univ., West Long Branch, NJ (United States)], Mahmood, Shayan [Univ. of Southern California, Los Angeles, CA (United States)], Verma, Riva [Univ. of Southern California, Los Angeles, CA (United States)], Georgia, Senta [Univ. of Southern California, Los Angeles, CA (United States)], Loconte, Valentina [Univ. of California, San Francisco, CA (United States); Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States); Harwell Science and Innovation Campus, Didcot (United Kingdom). Diamond Light Source, Ltd.], White, Kate L. [Univ. of Southern California, Los Angeles, CA (United States)] (ORCID:0000000188949621). 2025-08-26. Secretory stimuli distinctly regulate insulin secretory granule maturation through structural remodeling. https://doi.org/10.1016/j.str.2025.07.022
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