Altered cell-cell contacts in diabetic small intestine (Articulo completo en revisión)

HONORÉ S. M.; ZELARAYÁN L. C.; GENTA S. B.; VILLECCO E. I.; SÁNCHEZ S. S.

CELL AND TISSUE RESEARCH

Springer

Año: 2011 p. 1 - 45

0302-766X

Intestinal dysfunction is one of the clinical complications of diabetes. To better understand the impact of hyperglycemia on intestinal intercellular communications, we analyzed the expression of gap junctions (GJs) and N-cadherin/â-catenin complex in an experimental model of diabetes in rodents. High glucose down-regulated junctions in the mucosa and muscle layers of the intestine at early stages of the disease. Reduced expression of Cx43 and Cx45 proteins and aberrant cytoplasmic localization was determined in the mucosa layer and in the myenteric plexus cells. Results indicated that diabetes produced a Cx43 dephosphorilation. This could lead to an intracytoplasmic localization of this protein with a consequent loss of functional form. In the muscle layer the decreased in gap junction intercellular communication between smooth muscle cells exposed to high glucose was associated with a loss of Cx43 from the plasma membrane, as demonstrated by immunohistochemistry. Functional GJ requires appropriate cell adhesion mediated by the cadherin/catenin complex. Diabetic injury produced a significantly reduction in the N-cadherin/â-catenin complex contributing to abnormal intestinal cell-cell interactions. We propose that altered junctional adhesion molecules play a significant role at early stages of diabetic intestinal pathogenesis.