Journal article
Loss of the Golgi-localized v-ATPase subunit does not alter insulin granule formation or pancreatic islet β-cell function
American journal of physiology: endocrinology and metabolism, Vol.326(3), pp.E245-E257
03/01/2024
DOI: 10.1152/ajpendo.00342.2023
PMCID: PMC11193524
PMID: 38265287
Abstract
Delayed Golgi export of proinsulin has recently been identified as an underlying mechanism leading to insulin granule loss and β-cell secretory defects in Type 2 diabetes (T2D). Because acidification of the Golgi lumen is critical for proinsulin sorting and delivery into the budding secretory granule, we reasoned that dysregulation of Golgi pH may contribute to proinsulin trafficking defects. In this report, we examined pH regulation of the Golgi and identified a partial alkalinization of the Golgi lumen in a diabetes model. To further explore this, we generated a β-cell specific KO of the v0a2 subunit of the v-ATPase pump, which anchors the v-ATPase to the Golgi membrane. While loss of v0a2 partially neutralized Golgi pH and was accompanied by distension of the Golgi cisternae, proinsulin export from the Golgi and insulin granule formation were not affected. Furthermore, β-cell function was well-preserved. β-cell v0a2 KO mice exhibited normal glucose tolerance in both sexes, no genotypic difference to diet-induced obesity, and normal insulin secretory responses. Collectively, our data demonstrate the v0a2 subunit contributes to β-cell Golgi pH regulation but suggest that additional disturbances to Golgi structure and function contribute to proinsulin trafficking defects in diabetes.
Details
- Title: Subtitle
- Loss of the Golgi-localized v-ATPase subunit does not alter insulin granule formation or pancreatic islet β-cell function
- Creators
- Cierra K Boyer - University of IowaSandra E Blom - University of IowaAshleigh E Machado - Internal Medicine, University of Iowa, United StatesKristen E Rohli - University of IowaMichelle E Maxson - SickKids FoundationSamuel B Stephens - University of Iowa
- Resource Type
- Journal article
- Publication Details
- American journal of physiology: endocrinology and metabolism, Vol.326(3), pp.E245-E257
- DOI
- 10.1152/ajpendo.00342.2023
- PMID
- 38265287
- PMCID
- PMC11193524
- NLM abbreviation
- Am J Physiol Endocrinol Metab
- eISSN
- 1522-1555
- Grant note
- W81XWH-20-1-0200 / U.S. Department of Defense (DOD) T32GM145441 / HHS | National Institutes of Health (NIH) T32GM008629 / HHS | National Institutes of Health (NIH)
- Language
- English
- Electronic publication date
- 01/24/2024
- Date published
- 03/01/2024
- Academic Unit
- Fraternal Order of Eagles Diabetes Research Center; Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984548853902771
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