Different metabolic responses in alpha, beta and delta-cells of the islet of Langerhans monitored by redox confocal microscopy
Ivan Quesada 1*, Mariana G. Todorova 1 and Bernat Soria 1
1 Miguel Hernandez University
* To whom correspondence should be addressed. E-mail: ivanq{at}umh.es.
Submitted on July 5, 2005
Revised on August 26, 2005
Accepted on 19 December 2005
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Abstract |
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Blood glucose homeostasis is mainly achieved by the coordinated function of pancreatic alpha, beta and delta-cells, which secrete glucagon, insulin and somatostatin, respectively. Each cell type responds to glucose changes with different secretion patterns. Currently, considerable information can be found about the signal transduction mechanisms that lead to glucose-mediated insulin release in the pancreatic beta-cell, being mitochondrial activation an essential step. Increases in glucose stimulate the mitochondrial metabolism, activating the tricarboxylic acid cycle and raising the source of redox electron carrier molecules needed for respiratory ATP synthesis. However, little is known about the glucose-induced mitochondrial response of non-beta-cells and its role in the stimulus-secretion coupling process. This limited information is probably a result of the scarcity of these cells in the islet, the lack of identification patterns and the technical limitations of conventional methods. In this study, we have used FAD redox confocal microscopy as a non-invasive technique to specifically monitor mitochondrial redox responses in immunoidentified alpha, beta and delta-cells in freshly isolated intact islets and in dispersed cultured cells. We have shown that glucose provokes metabolic changes in beta and delta-cell populations in a dose-dependent manner. Conversely, no significant responses were observed in alpha-cells, despite the sensitivity of their metabolism to drugs acting on the mitochondrial function, and their intact ability to develop calcium signals. Identical results were obtained in islets and in cultures of dispersed cells. Our findings indicate metabolic differences in glucose utilization among the alpha, beta and delta-cell populations, which might be important in the signal transduction events that lead to hormone release.
Key Words:
alpha-cells, calcium oscillations, confocal microscopy, delta-cells, insulin, islet of Langerhans
