Expression of the glucose-sensing receptor T1R3 in pancreatic islet: changes in the expression levels in various nutritional and metabolic states.

ABSTRACT

We reported recently that the taste type 1 receptor 3 (T1R3), a subunit of the sweet taste receptor, functions as a cell-surface glucose-sensing receptor in pancreatic ß-cells. In the present study, we investigated the expression of T1R3 in pancreatic islets. mRNA for T1R2 and T1R3 was detected in mouse pancreatic islets. Quantitatively, the mRNA expression level of T1R2 was less than 1% of that of T1R3. Immunohistochemically, T1R3 was abundantly expressed in mouse islets whereas T1R2 was barely detected. Most immunoreactive T1R3 was colocalized with insulin and almost all ß-cells were positive for T1R3. In addition, T1R3 was expressed in some portion of α-cells. Immunoreactivity of T1R3 in ß-cells was markedly reduced in fed mice compared to those in fasting mice. In contrast, mRNA for T1R3 was not different in islets of fasting and fed mice. Glucose-induced insulin-secretion was higher in islets obtained from fasting mice compared to those from fed mice. The expression of T1R3 was markedly reduced in islets of ob/ob mice compared to those of control mice. Similarly, the expression of T1R3 was reduced in islet of db/db mice. In addition, the expression of T1R3 was markedly reduced in ß-cells of fatty diabetic rats and GK rats, models of obese and non-obese type 2 diabetes, respectively. These results indicate that T1R3 is expressed mainly in ß-cells and the expression levels are different depending upon the nutritional and metabolic conditions.