Sodium-glucose transporters SGLT1 and SGLT2 in equine renal, hepatic and pancreatic tissue.

BACKGROUND: Insulin dysregulation is a hallmark of equine metabolic syndrome (EMS), and in recent years, pharmacological treatment with sodium-dependent glucose transporter 2 inhibitors (SGLT2i) have shown promise in reducing the risk of hyperinsulinemia-associated laminitis in horses diagnosed with EMS. In humans and laboratory animals, this transporter protein is responsible for the majority of renal tubular glucose reabsorption, however, the presence of this and the related sodium-dependent glucose transporter 1 (SGLT1) have not yet been studied in equine kidneys. Additionally, studies in humans and laboratory animals have documented the presence of SGLT1 and SGLT2 also in hepatic and pancreatic tissue, which may explain extra-renal treatment effects of SGLT2i. Since the specificity towards SGLT2 and SGLT1 differ between the various SGLT2i drugs currently in use in horses, investigating SGLT2 and SGLT1 protein expression in equine tissues may help understanding potential differences in treatment effect and/or side effect profile between substances. The objective of this study was therefore to evaluate the presence of SGLT2 and SGLT1 in equine kidneys, liver and pancreas. RESULTS: Tissue samples from ten healthy Norwegian/Swedish Coldblood Trotters were collected. Using immunohistochemistry with antibodies raised against human SGLT1 and SGLT2, a strong SGLT2 antibody signal was present in the apical membranes of epithelial cells in the cortical labyrinth of the kidney, while SGLT1 positive cells were predominantly found in medullary rays. Both of these results concur with those in humans and rats. Using electron microscopy, ultrastructural localisation of positive SGLT2 antibody signal was confirmed to the microvilli of tubular epithelial cells. Positive SGLT2 signal was also detected in periportal hepatocytes and in cells within islet of Langerhans in the endocrine pancreas. Positive SGLT1 signal was seen in cholangiocytes in the portal areas of the liver, and in Kuppfer cells. CONCLUSIONS: The present study confirms presence of SGLT2 and SGLT1 in the equine kidney, localized to the proximal tubule. Also, presence of SGLT2 in the liver and pancreas, suggest that SGLT2i may have both renal and extrarenal effects.