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Different Metabolic Responses in -, ß-, and -Cells of the Islet of Langerhans Monitored by Redox Confocal Microscopy

Institute of Bioengineering, Miguel Hernandez University, Sant Joan d' Alacant, Spain

Correspondence: Address reprint requests to Ivan Quesada, PhD, Institute of Bioengineering, Miguel Hernandez University, Ctra. N-332, Km. 87, 03550 Sant Joan d' Alacant, Spain. Tel.: 34-96-591 9217; Fax: 34-96-591 9546; E-mail: ivanq{at}umh.es.

Blood glucose homeostasis is mainly achieved by the coordinated function of pancreatic -, ß-, and -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 ß-cell, mitochondrial activation being 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-ß-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 used flavin adenine dinucleotide redox confocal microscopy as a noninvasive technique to specifically monitor mitochondrial redox responses in immunoidentified -, ß-, and -cells in freshly isolated intact islets and in dispersed cultured cells. We have shown that glucose provokes metabolic changes in ß- and -cell populations in a dose-dependent manner. Conversely, no significant responses were observed in -cells, despite the sensitivity of their metabolism to drugs acting on the mitochondrial function, and their intact ability to develop Ca²⁺ signals. Identical results were obtained in islets and in cultures of dispersed cells. Our findings indicate metabolic differences in glucose utilization among the -, ß-, and -cell populations, which might be important in the signal transduction events that lead to hormone release.

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