Proceedings of The Physiological Society

Newcastle University (2009) Proc Physiol Soc 16, PC35

Poster Communications

Diabetes mellitus and gene expression of ‘sweet’ taste receptors in the jejunum and kidney

H. Chichger1, J. Marks1, E. S. Debnam1, R. Unwin1

1. Neuroscience, Physiology and Pharmacology, UCL, London, United Kingdom.


The facilitative glucose transporter, GLUT2, is normally poorly expressed at the jejunal brush-border membrane (BBM), but levels increase markedly in response to the high luminal glucose levels that occur during digestion (Kellett et al., 2000). Recently, the sweet taste receptors T1R2 and TIR3 have been shown to detect high levels of glucose in the jejunal lumen, and to act as signals for GLUT2 insertion at the BBM (Mace et al., 2007). In the kidney, raised levels of glucose are present in the proximal tubular (PT) lumen in diabetic hyperglycaemia, and we have shown that GLUT2 is highly expressed at the PT BBM in streptozotocin (STZ)-diabetic rats and accounts for the increased BBM glucose uptake that occurs in this model (Marks et al., 2003). Unlike the small intestine, expression of taste receptors in the kidney, and their possible involvement in BBM GLUT2 expression, is unknown. The aims of our study were twofold: first to assess whether taste receptors are expressed in kidney cortex; second to determine the effect of type 1 diabetes mellitus (DM) on T1R expression in both jejunum and kidney. DM was induced in Sprague-Dawley rats by treatment with streptozotocin (STZ, 55mg.kg-1, i.v). Jejunal sections and kidneys were removed from anaesthetised (pentobarbitone sodium, 55mg.kg-1, i.p.) animals 10 and 30 d after STZ, and from control animals. RNA was extracted from jejunal mucosal scrapes and kidney cortex. T1R1, TIR2 and TIR3 and β-actin transcripts were analysed by real-time PCR. The comparative delta delta Ct method was used to calculate the relative gene expression. In kidneys from non-diabetic animals all three taste receptors were expressed; however, T1R1 and TIR3 were highly expressed compared with T1R2, a pattern which was also seen in jejunum. 10 d diabetes reduced renal expression of TIR1 and TIR3 by 97% (p<0.01) and 55% (p>0.05), respectively. In contrast, 30 d DM increased renal T1R1 and TIR3 mRNA levels by 30% and 22% (p<0.05 and p>0.05 respectively). In jejunum, 10 d diabetes reduced TIR1 and TIR3 mRNA expression by 78% (p>0.05) and 65% (p<0.005), respectively; whereas 30 d diabetes reduced the expression of T1R1 by 28% (p>0.05), but increased that of TIR3 (34%, p<0.05). Our data indicate for the first time that gene expression of sweet taste receptors occurs in the kidney. Diabetes caused complex changes in expression of TIR1 and TIR3 in both kidney and jejunum. The relationship between taste receptor expression and diabetes-induced appearance of GLUT2 at the BBM in both tissues is under study.

Where applicable, experiments conform with Society ethical requirements