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- Title
Loss of Connexin36 Channels Alters β-Cell Coupling, Islet Synchronization of Glucose-Induced Ca<sup>2+</sup> and Insulin Oscillations, and Basal Insulin Release.
- Authors
Ravier, Magalie A.; Güldenagel, Martin; Charollais, Anne; Gjinovci, Asllan; Caille, Dorothée; Söhl, Goran; Wollheim, Claes B.; Willecke, Klaus; Henquin, Jean-Claude; Meda, Paolo
- Abstract
Normal insulin secretion requires the coordinated functioning of β-cells within pancreatic islets. This coordination depends on a communications network that involves the interaction of β-cells with extracellular signals and neighboring cells. In particular, adjacent β-cells are coupled via channels made of connexin36 (Cx36). To assess the function of this protein, we investigated islets of transgenic mice in which the Cx36 gene was disrupted by homologous recombination. We observed that compared with wild-type and heterozygous littermates that expressed Cx36 and behaved as nontransgenic controls, mice homozygous for the Cx36 deletion (Cx36-/-) featured β-cells devoid of gap junctions and failing to exchange microinjected Lucifer yellow. During glucose stimulation, islets of Cx36-/- mice did not display the regular oscillations of intracellular calcium concentrations ([Ca2+]i) seen in controls due to the loss of cell-to-cell synchronization of [Ca2+]i changes. The same islets did not release insulin in a pulsatile fashion, even though the overall output of the hormone in response to glucose stimulation was normal. However, under nonstimulatory conditions, islets lacking Cx36 showed increased basal release of insulin. These data show that Cx36-dependent signaling is essential for the proper functioning of β-cells, particularly for the pulsatility of [Ca2+]i and insulin secretion during glucose stimulation. Diabetes 54:1798-1807, 2005
- Subjects
CONNEXINS; PANCREATIC beta cells; INSULIN; ISLANDS of Langerhans; TRANSGENIC mice; GENES
- Publication
Diabetes, 2005, Vol 54, Issue 6, p1798
- ISSN
0012-1797
- Publication type
Article
- DOI
10.2337/diabetes.54.6.1798