Journal article
Microtubules regulate pancreatic beta-cell heterogeneity via spatiotemporal control of insulin secretion hot spots
eLife, Vol.10, e59912
11/16/2021
DOI: 10.7554/eLife.59912
PMCID: PMC8635970
PMID: 34783306
Abstract
Heterogeneity of glucose-stimulated insulin secretion (GSIS) in pancreatic islets is physiologically important but poorly understood. Here, we utilize mouse islets to determine how microtubules (MTs) affect secretion toward the vascular extracellular matrix at single cell and subcellular levels. Our data indicate that MT stability in the beta-cell population is heterogenous, and that GSIS is suppressed in cells with highly stable MTs. Consistently, MT hyper-stabilization prevents, and MT depolymerization promotes the capacity of single beta-cell for GSIS. Analysis of spatiotemporal patterns of secretion events shows that MT depolymerization activates otherwise dormant beta-cells via initiation of secretion clusters (hot spots). MT depolymerization also enhances secretion from individual cells, introducing both additional clusters and scattered events. Interestingly, without MTs, the timing of clustered secretion is dysregulated, extending the first phase of GSIS and causing oversecretion. In contrast, glucose-induced Ca2+ influx was not affected by MT depolymerization yet required for secretion under these conditions, indicating that MT-dependent regulation of secretion hot spots acts in parallel with Ca2+ signaling. Our findings uncover a novel MT function in tuning insulin secretion hot spots, which leads to accurately measured and timed response to glucose stimuli and promotes functional beta-cell heterogeneity.
Details
- Title: Subtitle
- Microtubules regulate pancreatic beta-cell heterogeneity via spatiotemporal control of insulin secretion hot spots
- Creators
- Kathryn P. Trogden - Vanderbilt UniversityJustin Lee - Vanderbilt UniversityKai M. Bracey - Vanderbilt UniversityKung-Hsien Ho - Vanderbilt UniversityHudson McKinney - Vanderbilt UniversityXiaodong Zhu - Vanderbilt UniversityGoker Arpag - Vanderbilt UniversityThomas G. Folland - Vanderbilt UniversityAnna B. Osipovich - Vanderbilt UniversityMark A. Magnuson - Vanderbilt UniversityMarija Zanic - Vanderbilt UniversityGuoqiang Gu - Vanderbilt UniversityWilliam R. Holmes - Vanderbilt UniversityIrina Kaverina - Vanderbilt University
- Resource Type
- Journal article
- Publication Details
- eLife, Vol.10, e59912
- DOI
- 10.7554/eLife.59912
- PMID
- 34783306
- PMCID
- PMC8635970
- NLM abbreviation
- Elife
- ISSN
- 2050-084X
- eISSN
- 2050-084X
- Publisher
- eLIFE SCIENCES PUBL LTD
- Number of pages
- 33
- Grant note
- T32 DK07061; 1F32DK117529; R35-GM127098; R01-DK65949; DMS1562078; R01-DK106228; R35-GM119552; F31 DK122650 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Language
- English
- Date published
- 11/16/2021
- Academic Unit
- Physics and Astronomy
- Record Identifier
- 9984429043502771
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