Distinct insulin granule subpopulations implicated in the secretory pathology of diabetes types 1 and 2
- University of Virginia, United States
- University of Michigan, United States
- Max Planck Institute of Biophysical Chemistry, Germany
Abstract
Insulin secretion from β-cells is reduced at the onset of type-1 and during type-2 diabetes. Although inflammation and metabolic dysfunction of β-cells elicit secretory defects associated with type-1 or type-2 diabetes, accompanying changes to insulin granules have not been established. To address this, we performed detailed functional analyses of insulin granules purified from cells subjected to model treatments that mimic type-1 and type-2 diabetic conditions and discovered striking shifts in calcium affinities and fusion characteristics. We show that this behavior is correlated with two subpopulations of insulin granules whose relative abundance is differentially shifted depending on diabetic model condition. The two types of granules have different release characteristics, distinct lipid and protein compositions, and package different secretory contents alongside insulin. This complexity of β-cell secretory physiology establishes a direct link between granule subpopulation and type of diabetes and leads to a revised model of secretory changes in the diabetogenic process.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
Article and author information
Author details
Alex JB Kreutzberger
Funding
National Institutes of Health (P01 GM072694)
- Lukas K Tamm
National Institutes of Health (R01 DK091296)
- J David Castle
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Suzanne R Pfeffer, Stanford University School of Medicine, United States
Version history
- Received: August 26, 2020
- Accepted: November 6, 2020
- Accepted Manuscript published: November 9, 2020 (version 1)
- Version of Record published: December 15, 2020 (version 2)
Copyright
© 2020, Kreutzberger et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Distinct insulin granule subpopulations implicated in the secretory pathology of diabetes types 1 and 2
eLife 9:e62506.
https://doi.org/10.7554/eLife.62506
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