Poster Presentation Australian Diabetes Society and the Australian Diabetes Educators Association Annual Scientific Meeting 2014

Sodium glucose co-transporter 2 is not expressed in rat pancreatic islets. (#245)

Christos N Joannides 1 , Maria Stathopoulos 1 , Salvatore P Mangiafico 1 , Benjamin J Lamont 1 , Sofianos Andrikopoulos 1
  1. University of Melbourne, Heidelberg, VIC, Australia

A new class of oral antidiabetic drugs known as sodium glucose co-transporter 2 (SGLT2) inhibitors have recently been approved for use in Australia. These drugs help to reduce hyperglycaemia by limiting glucose reabsorption in the kidney and therefore increase urinary glucose excretion. Since this novel class of drugs impart their effects by competing for SGLT2 in the kidney, we wanted to know whether SGLT2 is expressed in other tissues which may contribute to the beneficial effects seen in patients taking this drug. To test this we utilised a glucose intolerant rat model, the PEPCK transgenic rat. The aims of this study were to measure gene expression levels of the key glucose transporter channels: GLUT2, SGLT1 and SGLT2 in (i) isolated rat islets exposed to 11.1mM or 20mM glucose conditions for 24hr; (ii) liver; and (iii) kidney. Our results show that (i) incubating islets in 20mM glucose for 24hr significantly increased levels of GLUT2 (2.0 ± 0.4 vs. 1.0 ± 0.1 arbitrary units, p = 0.04, n = 5) but resulted in undetectable levels of SGLT1 (undetectable vs. 1.0 ± 0.3, n = 4) and undetectable levels of SGLT2 in islets incubated in either conditions; (ii) compared with control, PEPCK transgenic rat livers showed significantly elevated GLUT2 (2.0 ± 0.2 vs. 1.0 ± 0.1, p = 0.003, n = 4-5), no differences in SGLT1 (1.6 ± 0.3 vs. 1.0 ± 0.2, p = 0.1, n = 4-5) and undetectable levels of SGLT2; and (iii) no differences in either GLUT2 (0.8 ± 0.2 vs. 1.0 ± 0.2, p = 0.4, n = 4) or SGLT2 levels (1.7 ± 0.2 vs. 1.0 ± 0.2, p = 0.08, n = 3-4) but reduced levels of SGLT1 (0.4 ± 0.07 vs. 1.0 ± 0.04, p = 0.0003, n = 4) in the kidney. We conclude that SGLT2 is not expressed in pancreatic rat islets or in the liver of a rat model of glucose intolerance.