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First published online 15 April 2003
doi: 10.1242/jcs.00442

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Lentivirus-mediated transduction of connexin cDNAs shows level- and isoform-specific alterations in insulin secretion of primary pancreatic ß-cells

¹ Department of Morphology, University of Geneva Medical School, 1211 Geneva 4, Switzerland
² Department of Genetics and Microbiology, University of Geneva Medical School, 1211 Geneva 4, Switzerland

^* Author for correspondence (e-mail: david.caton{at}medecine.unige.ch)

Accepted 25 February 2003

We have generated novel lentiviral vectors to integrate various connexin cDNAs into primary, non-dividing cells. We have used these vectors to test whether proper control of insulin secretion depends on a specific connexin isoform and/or on its level of expression. We have observed that transduced connexin32, connexin36 and connexin43 were expressed by primary adult ß-cells at membrane interfaces, were packed into typical gap junction plaques and formed functional channels that allowed a variable coupling, depending on the type and level of connexin expressed. The infected cells spontaneously reaggregated into three-dimensional pseudo-islet organs that could be maintained in culture. We have found that pseudo-islets made by cells transduced with either GFP- or connexin43-expressing lentivirus released insulin in response to various secretagogues similarly to controls. By contrast, pseudo-islets made by cells expressing connexin32, a connexin exogenous to pancreatic islets, or over-expressing connexin36, the endogenous islet connexin, featured a marked decrease in the secretory response to glucose. The data show: (1) that lentiviral vectors allow stable modulation of various connexin in primary, non-proliferating cells; (2) that specific connexin isoforms affect insulin secretion differently; and (3) that adequate levels of coupling via connexin36 channels are required for proper ß-cell function.

Key words: Cx32, Cx36, Cx43, Gap junctions, Lentiviral vectors, Pancreatic ß-cells

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