Sweet Taste-Sensing Receptors Expressed in Pancreatic beta-Cells: Sweet Molecules Act as Biased Agonists

The sweet taste receptors present in the taste buds are heterodimers comprised of T1R2 and T1R3. This receptor is also expressed in pancreatic beta-cells. When the expression of receptor subunits is determined in beta-cells by quantitative reverse transcription polymerase chain reaction, the mRNA expression level of T1R2 is extremely low compared to that of T1R3. In fact, the expression of T1R2 is undetectable at the protein level. Furthermore, knockdown of T1R2 does not affect the effect of sweet molecules, whereas knockdown of T1R3 markedly attenuates the effect of sweet molecules. Consequently, a homodimer of T1R3 functions as a receptor sensing sweet molecules in beta-cells, which we designate as sweet taste-sensing receptors (STSRs). Various sweet molecules activate STSR in beta-cells and augment insulin secretion. With regard to intracellular signals, sweet molecules act on STSRs and increase cytoplasmic Ca2+ and/or cyclic AMP (cAMP). Specifically, when an STSR is stimulated by one of four different sweet molecules (sucralose, acesulfame potassium, sodium saccharin, or glycyrrhizin), distinct signaling pathways are activated. Patterns of changes in cytoplasmic Ca2+ and/or cAMP induced by these sweet molecules are all different from each other. Hence, sweet molecules activate STSRs by acting as biased agonists.

The study on opioid switching for the purpose of the quality of life improvement in the gynecologic cancer

Oxycodone controlled-release (CR) tablets are used as a first-line opioid analgesic for cancer pain. However, use of oxycodone CR tablets is associated with toxicities such as drowsiness and constipation, leading to deterioration of the quality of life (QOL), especially in patients with gynecologic cancer. In contrast, fentanyl has a superior toxicity profile while still showing a strong analgesic effect. Although fentanyl has been approved for switching from opioid, there have been no Japanese studies of patients with gynecologic cancer who were switched to transdermal fentanyl after experiencing toxicity during therapy with oxycodone CR. More importantly early introduction of palliative therapy for pain has not been adopted routinely in the management of gynecologic cancer. Thus, it appears that treatment for patients with gynecologic cancer remains unsatisfactory at present. We conducted research into improvement of the toxicity profile and pain control with the aim of improving QOL for patients with gynecologic cancer. We showed that pain, drowsiness, and constipation could be significantly improved in gynecologic cancer patients as a result of switching to transdermal fentanyl therapy at an early stage.

The Role of the Sweet Taste Receptor in Enteroendocrine Cells and Pancreatic beta-Cells

The sweet taste receptor is expressed in taste cells located in taste buds of the tongue. This receptor senses sweet substances in the oral cavity, activates taste cells, and transmits the taste signals to adjacent neurons. The sweet taste receptor is a heterodimer of two G protein-coupled receptors, T1R2 and T1R3. Recent studies have shown that this receptor is also expressed in the extragustatory system, including the gastrointestinal tract, pancreatic beta-cells, and glucose-responsive neurons in the brain. In the intestine, the sweet taste receptor regulates secretion of incretin hormones and glucose uptake from the lumen. In beta-cells, activation of the sweet taste receptor leads to stimulation of insulin secretion. Collectively, the sweet taste receptor plays an important role in recognition and metabolism of energy sources in the body.