Abstract
To assess whether connexin (Cx) expression contributes to insulin secretion, we have investigated normal and tumoral insulin-producing cells for connexins, gap junctions, and coupling. We have found that the glucose-sensitive cells of pancreatic islets and of a rat insulinoma are functionally coupled by gap junctions made of Cx43. In contrast, cells of several lines secreting insulin abnormally do not express Cx43, gap junctions, and coupling. After correction of these defects by stable transfection of Cx43 cDNA, cells expressing modest levels of Cx43 and coupling, as observed in native beta-cells, showed an expression of the insulin gene and an insulin content that were markedly elevated, compared with those observed in both wild-type (uncoupled) cells and in transfected cells overexpressing Cx43. These findings indicate that adequate levels of Cx-mediated coupling are required for proper insulin production and storage.
Highlights
To assess whether connexin (Cx) expression contributes to insulin secretion, we have investigated normal and tumoral insulin-producing cells for connexins, gap junctions, and coupling
We show that correction of these defects by stable transfection of the gene sequence coding for Cx43 (Beyer et al, 1987; Kumar and Gilula, 1992), modified the expression of the insulin gene, as well as the storage of insulin, in a way dependent on junctional coupling mediated by connexin expression
In both islet and purified cell samples, the amplification of the Cx43 cDNA product increased in parallel with that of 13-cell specific glucokinase, and wassignificantly less abundant than that observed in samples of heart (Fig. 1), the organ in which Cx43 was originally identified
Summary
To assess whether connexin (Cx) expression contributes to insulin secretion, we have investigated normal and tumoral insulin-producing cells for connexins, gap junctions, and coupling. When 13-cellsare separated, insulin biosynthesis and secretion are markedly reduced, in response to glucose concentrations that physiologically stimulate pancreatic islets These changes, and their rapid correction after cell reaggregation, suggest that a crucial regulatory mechanism of insulin secretion depends on [3-cell contacts (Lernmark, 1974; Halban et al, 1982; Salomon and Meda, 1986; Bosco et al, 1989; Philippe et al, 1992). These novel findings indicate that adequate expression of connexins and junctional coupling is required for proper functioning of insulin-producing cells
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