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Characterization of central nuclei involved in sympathetic activity modulation to salivary glands: control of salivary glucose concentration and flux in hypertensive and diabetic rats.

Grant number: 09/16502-0
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): April 01, 2010
Effective date (End): February 28, 2011
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:Ubiratan Fabres Machado
Grantee:Robinson Sabino da Silva
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:07/50554-1 - Glucose transporters and diabetes mellitus: contribution to the knowledge of glycemic control and chronic diseases development, AP.TEM


The dysfunctions of salivary glands (SG) that have been described in diabetic and hypertensive patients may correlate with changes in subcellular localization of glucose transporters SGLT1 and GLUT1 in parotid and submandibular, but the true mechanisms of these functional impairments have not been identified yet. Despite the presence of SGLT1 and GLUT1 in different cells of the SG, the exact mechanism by which glucose moves from the blood to the final saliva is still unknown, and the presence of GLUT2 and SGLT2 transporters could contribute to understand the routes of glucose in this territory. Additionally, given the recent observation that SGLT1 is a powerful water transporter, and our observation of its presence in luminal membrane of ductal cells, the SGLT1 regulation may represent an important mechanism for controlling the volume of saliva in pathophysiological conditions. Sympathetic activity to the SG is essential in the control of salivary secretion and modulation of gene expression. It is known that the sympathetic innervation of SG involves preganglionic neurons, that project from the first thoracic segments of the spinal cord, and then connect at synapse in the superior cervical ganglion; however the central origin of this pathway in unknown. We demonstrate that the activity of postganglionic sympathetic neurons that project into the SG is decreased in diabetic, and increased in hypertensive animals. We also found that sympathetic nerve activity to the SG increased in parallel with the increase in blood pressure induced by phenylephrine, indicating modulation by baroreceptors. Therefore, the objective of this study is to investigate in diabetic and hypertensive rats: (i) whether the regulation of SGLT1, per se, induces variations in salivary flux, (ii) the presence and regulation of GLUT2 and SGLT2 in SG, and their role on glucose fluxes, and (iii) the central nuclei and neural pathways involved in the control of postganglionic sympathetic activity to the SG. These information should contribute to knowledge of the underlying mechanism determinants of xerostomia present in diabetic and/or hypertensive subjects, as well as the potential role of autonomic neuropathy in these changes.

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
SABINO-SILVA, ROBINSON; OKAMOTO, MARISTELA MITIKO; DAVID-SILVA, ALINE; MORI, ROSANA CRISTINA; FREITAS, HELAYNE SOARES; MACHADO, UBIRATAN FABRES. Increased SGLT1 expression in salivary gland ductal cells correlates with hyposalivation in diabetic and hypertensive rats. DIABETOLOGY & METABOLIC SYNDROME, v. 5, OCT 24 2013. Web of Science Citations: 8.
SABINO-SILVA, ROBINSON; CERONI, ALEXANDRE; KOGANEZAWA, TADACHIKA; MICHELINI, LISETE C.; MACHADO, UBIRATAN F.; ANTUNES, VAGNER R. Baroreceptor-mediated activation of sympathetic nerve activity to salivary glands. Physiology & Behavior, v. 107, n. 3, p. 390-396, OCT 10 2012. Web of Science Citations: 0.

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