Experimental Physiology http://ep.msubmit.net EP-RP-2015-085670R2 Title: Type II diabetes and related models of impaired glucose metabolism differentially regulate glucose transporters at the proximal tubule brush border Authors: Havovi Chichger Mark E Cleasby Kaila Srai Robert John Unwin E S Debnam Joanne Marks Author Conflict: No competing interests declared Running Title: GLUT2, SGLT1 and SGLT2 in diabetes-related disease Abstract: Objective: SGLT2 inhibitors are now in clinical use to reduce hyperglycemia in type II diabetes. However, renal glucose reabsorption across the brush border membrane (BBM) is not completely understood in diabetes. Increased consumption of a Western diet is strongly linked to type II diabetes. This study aimed to investigate the adaptations that occur in renal glucose transporters in response to experimental models of diet-induced insulin resistance. Research Design and Methods: The study used Goto-Kakizaki type II diabetic rats and normal rats rendered insulin resistant using junk-food or high-fat (HFD) diets. Levels of PKC-βI, GLUT2, SGLT1 and 2 were determined by western blotting of purified renal BBM. GLUT- and SGLT-mediated [3H]-glucose uptake by BBM vesicles was measured in the presence and absence of the SGLT inhibitor phlorizin. Results: GLUT- and SGLT- mediated glucose transport were elevated in type II diabetic rats, accompanied by increased expression of GLUT2, its upstream regulator PKC-βI, and SGLT1 protein. Disclaimer: This is a confidential document.