A atividade simpática regula, via proteína cinase A (PKA), a proteína cotransportadora Na+/glicose 1 (SGLT1) em glândula salivar: efeitos do Diabetes Mellitus e da hipertensão arterial.

Abstract

Sabino-Silva R. Na+/glucose cotransporter SGLT1 in the salivary glands of diabetic and hypertensive rats: role of sympathetic outflow and protein kinase A activity [PhD. thesis]. Sao Paulo: Instituto de Ciencias Biomedicas, Universidade de Sao Paulo; 2010. Salivary dysfunctions have been described in diabetic and hypertensive subjects. The stoichiometric relationship of transport capacity of the sodium glucose cotransporter 1 (SGLT1) protein is 2 Na:1 glucose:264 H2O molecules. We hypothesized that the sodium-glucose cotransporter 1 (SGLT1) participates in salivary dysfunctions, through the sympatheticand protein kinase A(PKA) induced regulation of SGLT1. The analysis were performed in Wistar Kyoto rats (WKY), diabetic WKY (WKY-D), spontaneously hypertensive rats (SHR), diabetic SHR (SHR-D). Rats were rendered diabetic (WKY-D or SHR-D) by a single intravenous injection of alloxan (40 mg/Kg body weight). The parotid and submandibular glands were harvested for SLC5A1 and SLC2A1 gene expression (RT-PCR) and SGLT1, GLUT1 and PKA protein content (Western blotting and/or immunohistochemistry) analysis. Moreover, sympathetic nerve activity to the salivary glands was measured in post-ganglionic fibers. Diabetes decreased the nerve activity in WKY and SHR (~50%, P<0.05), pointing out that it was 250% higher in SHR, as compared to WKY (P<0.001). The regulation of catalytic subunit of PKA was parallel to the sympathetic nerve activity. Plasma membrane SGLT1 protein content increased in SHR (~130%, p<0.001) and decreased in WKY-D (~50%, P<0.05), as compared with WKY. Moreover, in diabetic and/or hypertensive rats, imunohistochemical analysis showed increased SGLT1 protein in luminal membrane of ductal cells, where it may promote water uptake, reducing the salivary flow. Confirming that, nonstimulated salivary secretion was reduced (~50%, p<0.001) in WKY-D, SHR and SHR-D rats. No differences were observed in GLUT1 mRNA and protein in plasma membrane. The results show a highly coordinated regulation of sympathetic activity, catalytic subunit of PKA and SGLT1 protein in plasma membrane of acinar cells of salivary glands in diabetic, hypertensive or not, rats. Importantly, in luminal membrane of ductal cells SGLT1 protein increased inversely proportional to the nonstimulated salivary flux in diabetic and hypertensive rats. This indicates the water transporter role of SGLT1, and, by increasing salivary water reabsorption, may explain the hyposalivation complained by diabetic and hypertensive subjects.