Stimulus Secretion Coupling in Exocrine and Endocrine Cells

Low, Jiun-tsuen (2013). Stimulus Secretion Coupling in Exocrine and Endocrine Cells PhD Thesis, School of Biomedical Sciences, The University of Queensland.

       
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Author Low, Jiun-tsuen
Thesis Title Stimulus Secretion Coupling in Exocrine and Endocrine Cells
School, Centre or Institute School of Biomedical Sciences
Institution The University of Queensland
Publication date 2013-01-01
Thesis type PhD Thesis
Supervisor Peter Thorn
Wally Thomas
Total pages 176
Total colour pages 34
Total black and white pages 142
Language eng
Subjects 111601 Cell Physiology
0606 Physiology
Formatted abstract
It is well established that calcium is the main signal in triggering secretion in both excitable and non-excitable cells. Given a stimulant, calcium signals with different spatial profiles can be triggered. These calcium profiles are likely to be essential in modulating the secretion. Here, we have investigated the control and spatial distribution of exocytic events in exocrine and endocrine cells. Using high speed two-photon microscopy, we can record calcium signals and the precise spatial and temporal location of each individual granule fusion event.

In pancreatic acinar cells, I showed that there are long latencies between calcium elevation and exocytosis (>2 seconds), exclusion of exocytic events from the calcium release hot-spots, high calcium affinity (Kd=1.75μM). In addition, I also showed that number of exocytic events reduce in the presence of calcium chelator EGTA, and inability of triggering exocytosis by local calcium elevation. All these findings suggested that exocytic events triggered by calcium from intracellular calcium store are regulated by calcium microdomains.

In pancreatic β cells, published evidences suggest that calcium microdomains regulate the insulin granule exocytosis. I therefore focused on understanding how glucose controls insulin secretion from the many hundreds of β-cells within intact islets of Langerhans. Our results showed heterogeneity in the secretory response among β-cells. Analysis suggests that insulin granule fusion is strongly polarized and target to a limited area of the cell membrane that faces the vasculature. Glucose dose-dependently increases insulin granule fusion in this area but does not affect different types of post-fusion granule behaviours.
Keyword exocytosis
Two photon imaging
Exocrine
Endocrine
insulin
Acinar cell
Pancreatic islet

 
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Created: Fri, 17 Jan 2014, 12:06:41 EST by Jiun-tsuen Low on behalf of Scholarly Communication and Digitisation Service