Signaling pathways in diabetic gut

HONORÉ SM; GENTA SB; SÁNCHEZ SS

Guaruja, Sao Paulo, Brazil.

Congreso; 2nd International Meering of the Latin American of Developmental Biology; 2005

Gastrointestinal disorders are common complications in diabetic state. At the present the causes of the abnormal functions of the diabetic gut have not yet been completely understood. Inmunohistochemical, inmunoblotting, and electron microscopy techniques demonstrated alterations in the expression of extracellular matrix (ECM) and basement membrane molecules in muscular layer of induced-streptozotocin diabetic mice. The presence of fibronectin, vitronectin, collagen type III, IV and laminin 1 were higher than normal animals. In addition the expression of TGFb mRNA was signifigatly increased in the diabetic animals compared to controls This result suggest that TGFb play a role in the abnormal secretion of ECM components during hyperglycemic state. Moreover an increment in apoptosis level in the gut and a decrease in the myenteric ganglia density were observed under our experimental conditions. This results are in correlation with a significant decrease in the expression of Vasoactive intestinal polypeptide (VIP) mRNA, an inhibitory transmitter which mediate in the relaxation of the gastrointestinal muscle layer. A low tissue level of VIP in the jejunum of diabetic mice may contribute in part to the abnormal gut motility observed in diabetes. Considering that Bone morphogenetic proteins (BMPs) play important role in gut morphogenesis and regulate the specification and diferentiation of the developing Enteric Nervous System, the possible involvement of BMPs signaling in the observed changes was analyzed. Semicuantitative reverse transcription- polymerase chain reaction (RT-PCR) and in situ hybridization was performed for BMP2, BMP4, BMP type II, I receptors and Smad1. Changes were observed in levels of BMPs and in the type II receptor. This preliminary results raise the possibility that diabetic intestine could be under the influence of BMP during the pathogenesis.