Ca2+ is an important mediator of stimulus-secretion coupling in beta cells of the pancreatic islets, which secrete insulin in response to elevation in plasma glucose concentration. I studied the actions of two lipids, arachidonic acid (AA) and cholesterol, on enzymatically-dissociated single beta cells of rat and mouse, using cytosolic Ca2+ ([Ca2+]i) measurement in conjunction with whole-cell patch-clamp techniques.
AA, which is produced in the beta cell upon stimulation with either glucose or acetylcholine, was found to induce a large increase in [Ca2+]i that was dependent on both extracellular Ca2+ entry and intracellular Ca2+ release. Part of the AA-mediated extracellular Ca2+ entry was due to Ca2+ influx through the arachidonate-regulated Ca2+ (ARC) channels, which have not previously been reported in beta cells. The AA-mediated intracellular Ca2+ release was a result of Ca2+ mobilization from multiple inositol trisphosphate (IP3)-sensitive intracellular stores, including the endoplasmic reticulum (ER) and an acidic Ca2+ store that is probably the secretory granules. Therefore, in beta cells, the AA-mediated Ca2+ signal may amplify the [Ca2+]i rise induced by insulin secretagogues.
Cholesterol is an integral component of cellular membranes and an important regulator of cellular functions. However, elevation of cholesterol level in the pancreatic islets reduces glucose-stimulated insulin secretion. I found that cholesterol overload impairs the glucose-stimulated [Ca2+]i increase in beta cells by two major mechanisms: the first is a decrease in glucose-stimulated ATP production, which is partly mediated by a decrease in glucose uptake, and the second is the reduction of voltage-gated Ca2+ current density. These effects of cholesterol may partly account for the decreased insulin secretion that develops in patients with type II diabetes, who typically exhibit hypercholesterolemia.
In summary, different lipids may mediate beneficial or detrimental effects on Ca2+ regulation in rodent pancreatic beta cells.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:AEU.10048/1270 |
| Date | 11 1900 |
| Creators | Yeung-Yam-Wah, Valerie |
| Contributors | Tse, Amy (Centre for Neuroscience and Department of Pharmacology), Colmers, William F. (Centre for Neuroscience and Department of Pharmacology), Chaves, Elena Posse de (Department of Pharmacology), Karpinski, Edward (Department of Physiology), Braun, Andrew P. (Department of Physiology and Pharmacology, University of Calgary) |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | 1041155 bytes, application/pdf |
| Relation | Yeung-Yam-Wah V et al. Cell Calcium (Jan;47(1):77-83 (2010)) |
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