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Junctional communication of pancreatic β cells contributes to the control of insulin secretion and glucose tolerance
Anne Charollais, … , Pedro L. Herrera, Paolo Meda
Anne Charollais, … , Pedro L. Herrera, Paolo Meda
Published January 15, 2000
Citation Information: J Clin Invest. 2000;106(2):235-243. https://doi.org/10.1172/JCI9398.
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Article

Junctional communication of pancreatic β cells contributes to the control of insulin secretion and glucose tolerance

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Abstract

Proper insulin secretion requires the coordinated functioning of the numerous β cells that form pancreatic islets. This coordination depends on a network of communication mechanisms whereby β cells interact with extracellular signals and adjacent cells via connexin channels. To assess whether connexin-dependent communication plays a role in vivo, we have developed transgenic mice in which connexin 32 (Cx32), one of the vertebrate connexins found in the pancreas, is expressed in β cells. We show that the altered β-cell coupling that results from this expression causes reduced insulin secretion in response to physiologically relevant concentrations of glucose and abnormal tolerance to the sugar. These alterations were observed in spite of normal numbers of islets, increased insulin content, and preserved secretory response to glucose by individual β cells. Moreover, glucose-stimulated islets showed improved electrical synchronization of these cells and increased cytosolic levels of Ca2+. The results show that connexins contribute to the control of β cells in vivo and that their excess is detrimental for insulin secretion.

Authors

Anne Charollais, Asllan Gjinovci, Joachim Huarte, Juliette Bauquis, Angel Nadal, Franz Martín, Etelvina Andreu, Juan V. Sánchez-Andrés, Alessandra Calabrese, Domenico Bosco, Bernat Soria, Claes B. Wollheim, Pedro L. Herrera, Paolo Meda

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Figure 1

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Strategy for expressing Cx32 in pancreatic β cells. (a) A transgene that...
Strategy for expressing Cx32 in pancreatic β cells. (a) A transgene that contained part of the RIP, the second exon of Cx32 cDNA (Cx32; coding region limited by dots), and the coding region of human growth hormone gene (hGH) was microinjected into zygotic pronuclei, and surviving embryos were transferred into pseudopregnant foster mothers. (b) Transgenic mice were screened by Southern blot using probe 2. Compared with wild-type controls (W), which featured only the 7.6-kb endogenous gene (Cx32e), two positive founders were identified that also expressed the 1.5-kb transgene (Cx32t). These mice were backcrossed with C56BL/6 controls to generate the two independent lines B9 (lane 1) and D6 (lane 2). (c) The progeny were screened by PCR using primers along the hGH sequence. Heterozygous mice carrying the transgene (lanes 1, 3, and B) were distinguished from control littermates (lanes 2 and A) and wild-type controls (W) by the amplification of a 390-bp product (lane H, water; lane S, standards). (d) Heterozygous mice of the D6 line were further crossed to obtain a homozygous progeny. Mice carrying two alleles of the transgene (lanes 1 and 2) were distinguished from heterozygous littermates (lane 3) by hybridizing DNA with probe 1. Dot intensity was compared with that observed with DNA of mice from previous litters, whose homozygosity (lane C) or heterozygosity (lane B) had been biologically controlled by crossing with C57BL/6 controls.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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