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Experimental type II diabetes and related models of impaired glucose metabolism differentially regulate glucose transporters at the proximal tubule brush border membrane

Chichger, H; Cleasby, M; Srai, S; Unwin, R; Debnam, E; Marks, J; (2016) Experimental type II diabetes and related models of impaired glucose metabolism differentially regulate glucose transporters at the proximal tubule brush border membrane. Experimental Physiology , 101 (6) pp. 731-742. 10.1113/EP085670. Green open access

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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. Junk-food and HFD feeding also caused higher membrane expression of GLUT2 and its upstream regulator PKC-βI. However, the junk-food diet also increased SGLT1 and 2 levels at the proximal tubule BBM. Conclusions: Glucose reabsorption across the proximal tubule BBM, via GLUT2, SGLT1 and 2, is not solely dependent on glycemic status, but is also influenced by diet-induced changes in glucose metabolism. We conclude that different metabolic disturbances result in complex adaptation in renal glucose transporter protein levels and function.

Type: Article
Title: Experimental type II diabetes and related models of impaired glucose metabolism differentially regulate glucose transporters at the proximal tubule brush border membrane
Open access status: An open access version is available from UCL Discovery
DOI: 10.1113/EP085670
Publisher version: http://dx.doi.org/10.1113/EP085670
Language: English
Additional information: This is the peer reviewed version of the following article: Chichger, H; Cleasby, M; Srai, S; Unwin, R; Debnam, E; Marks, J; (2016) Experimental type II diabetes and related models of impaired glucose metabolism differentially regulate glucose transporters at the proximal tubule brush border membrane. Experimental Physiology, 101 (6) pp. 731-742, which has been published in final form at: http://dx.doi.org/10.1113/EP085670. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.
Keywords: Diabetes, kidney, Glucose transport
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
URI: http://discovery.ucl.ac.uk/id/eprint/1476974
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