Misregulated hormone secretion from the islets of Langerhans is central to the pathophysiology of Diabetes. While insulin plays a key role in glucose regulation and the modulation of secretion has immediate clinical implications, the importance of glucagon is increasingly acknowledged. However, the mechanisms that regulate glucagon secretion from alpha cells are still unclear. We utilized pseudo-islets reconstituted from dispersed islet cells to study alpha cells with and without various indirect effects from other islet cells. When cultured, both murine and human islet cells reassociated into pseudo-islets, which recovered normal glucose-regulated hormone secretion. We generated small (~40 µm) pseudo-islets using all of the islet cells, or only some of the cell types, which allowed us to characterize novel aspects of regulated hormone secretion. Our data suggest that the recovery of regulated glucagon secretion from alpha cells in small pseudo-islets depends upon the combined action of paracrine factors, like insulin and somatostatin, and juxtacrine signals between EphA4/7 on alpha cells and ephrins on beta cells. While these signals modulate different pathways, both appear to be required for proper inhibition of glucagon secretion in response to glucose. The improved understanding of the modulation of hormone secretion can provide novel therapeutic routes for the treatment of Diabetic individuals.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-03302017-082818 |
| Date | 07 April 2017 |
| Creators | Reissaus, Christopher Alan |
| Contributors | Maureen Gannon, Mark Magnuson, Richard O'Brien, David Jacobson, David Piston |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu/available/etd-03302017-082818/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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