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SORCS2 activity in pancreatic α-cells safeguards insulin granule formation and release from glucose-stressed β-cells

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Item Type:Article
Title:SORCS2 activity in pancreatic α-cells safeguards insulin granule formation and release from glucose-stressed β-cells
Creators Name:Kalnytska, O., Qvist, P., Kunz, S., Conrad, T., Willnow, T.E. and Schmidt, V.
Abstract:Sorting receptor SORCS2 is a stress-response factor protecting neurons from acute insults, such as during epilepsy. SORCS2 is also expressed in the pancreas, yet its action in this tissue remains unknown. Combining metabolic studies in SORCS2-deficient mice with ex vivo functional analyses and single-cell transcriptomics of pancreatic tissues, we identified a role for SORCS2 in protective stress response in pancreatic islets, essential to sustain insulin release. We show that SORCS2 is predominantly expressed in islet alpha cells. Loss of expression coincides with inability of these cells to produce osteopontin, a secreted factor that facilitates insulin release from stressed beta cells. In line with diminished osteopontin levels, beta cells in SORCS2-deficient islets show gene expression patterns indicative of aggravated cell stress, and exhibit defects in insulin granule maturation and a blunted glucose response. These findings corroborate a function for SORCS2 in protective stress response that extends to metabolism.
Keywords:Natural Sciences, Biological Sciences, Physiology, Endocrinology, Animals, Mice
Source:iScience
ISSN:2589-0042
Publisher:Cell Press
Volume:27
Number:1
Page Range:108725
Date:19 January 2024
Official Publication:https://doi.org/10.1016/j.isci.2023.108725
PubMed:View item in PubMed

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