Experimental diabetes alters cell-cell contacts in intestinal smooth muscle layer

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

Mar del Plata, Buenos Aires, Argentina

Congreso; XLIII Anual Meeting Sociedad Argentina de Investigacion en Bioquímica y Biología Molecular; 2007

Sociedad Argentina de Investigacion en Bioquímica y Biología Molecular

Intestinal dysfunction is a clinical complication of diabetes; however the molecular mechanisms of the intestinal motility disorders remain unclear. The smooth muscle layer of the intestine has a critical role in the motility. In diabetes altered intercellular cornmunications may account for some aspects of the enhanced contraction aml/or impaired relaxation of intestinal muscular layer resulting in a disturbed motility. To understand the impact of diabetes on muscle layer dysfunction, we analyzed gap junction and N-cadherin, b-catenin complex in an experimental model of diabetes in rodents. Jejunum samples ftom normal and diabetic animals were analyzed by RT-PCR, irnmunohistochemistry, westem-irnmunoblotting and confocal microscopy in order to determine these junctions. Our results show a decrease in Cx43 expression between smooth muscle cells during diabetes. Studies of colocalization ofCxs and c-kit suggested that Cx43 localization in the intersticial cell of Cajal network remain unchanged. In contrast, Cx45 shows a cytoplasmic strong reactivity in the diabetic myenteric plexus cells. Diabetes produces a significantly reduction ófN-cadherinl¡3-catenin complex. The alterations in gap junctions and N-cadherin/¡3-catenin complex suggest an impaired intercellular cornmunication between cells of the muscle layer which could be responsible forthe diabetic motility disfunction.