Increased SGLT1 expression in salivary gland ductal cells correlates with hyposalivation in diabetic and hypertensive rats

Abstract

Background: Oral health complications in diabetes and hypertension include decreased salivary secretion. The sodium-glucose cotransporter 1 (SGLT1) protein, which transports 1 glucose/2 Na+/264 H2O molecules, is described in salivary glands. We hypothesized that changes in SGLT1 expression in the luminal membrane of ductal cell may be related to an altered salivary flow.

Findings: By immunohistochemistry, we investigated SGLT1 expression in ductal cells of parotid and submandibular glands from Wistar Kyoto rats (WKY), diabetic WKY (WKY-D), spontaneously hypertensive rats (SHR) and diabetic SHR (SHR-D), as well as in parotid glands from WKY subjected to sympathetic stimulation, with or without previous propranolol blockade. Diabetes and hypertension decreased the salivary secretion and increased SGLT1 expression in the luminal membrane of ductal cells, and their association exacerbated the regulations observed. After 30 min of sympathetic stimulation, SGLT1 increased in the luminal membrane of ductal cells, and that was blocked by previous injection of propranolol.

Conclusions: SGLT1 expression increases in the luminal membrane of salivary gland ductal cells and the salivary flow decreases in diabetic and hypertensive rats, which may be related to sympathetic activity. This study highlights the water transporter role of SGLT1 in salivary glands, which, by increasing ductal water reabsorption, may explain the hyposalivation of diabetic and hypertensive subjects.

Figure 1

Immunolocalization of the SGLT1 protein in ductal cells of salivary glands. A. SGLT1 protein in ductal cells of submandibular glands of Wistar Kyoto rats (WKY), diabetic WKY (WKY-D), spontaneously hypertensive rats (SHR) and diabetic SHR (SHR-D). A to D: SGLT1 (green), F-actin (red) and nuclear marker (blue). E to H: only SGLT1 in green color. The SGLT1 protein in ductal cells of WKY can be seen in a very low intensity (A and E), whereas the SGLT1 immunoreactivity is clearly observed in WKY-D (B and F) and SHR (C and G); a further increase in SGLT1 can be observed in SHR-D (D and H). Arrowheads and arrows indicate the absence or presence of the SGLT1 protein in the luminal membrane of ductal cells; respectively. Scale bar, 20 μm. Images are representative of 4 animals in each group. B. SGLT1 protein in ductal cells of the parotid glands from Wistar-Kyoto rats that received physiological saline (A, B, E and F) or propranolol (C, D, G and H), and were subjected to 30-min sympathetic stimulation (B, F, D and H) or not (A, E, C and G). A to D: SGLT1 (green), F-actin (red) and nuclear marker (blue); E to H: only SGLT1 in green color. Scale bar, 20 μm. Arrowheads and arrows indicate the absence or presence of the SGLT1 protein in the luminal membrane of ductal cells; respectively. Images are representative of 4 animals in each group.