Molecular and cellular pharmacologyThe role of calcium in intracellular pathways of rutin in rat pancreatic islets: potential insulin secretagogue effect

Rutin is a flavonol glycoside with multiple biological activities and it has been demonstrated that rutin modulates glucose homeostasis. In pancreatic β-cell, an increase in intracellular calcium concentration triggers exocytosis and thus insulin secretion. The aim of the study reported herein was to investigate the effect of rutin associated intracellular pathways on Ca2+ uptake in isolated rat pancreatic islets. We focused on the acute effects of rutin on in vivo insulin secretion and the in vitro cellular signaling of pancreatic islets related to this effect. The results show that rutin significantly increased glucose-induced insulin secretion in an in vivo treatment. Moreover, it was demonstrated that rutin stimulated Ca2+ uptake after 10 min of incubation compared with the respective control group. The involvement of L-type voltage-dependent Ca2+ channels (L-VDCCs) was evidenced using nifedipine, while the use of glibenclamide and diazoxide demonstrated that the ATP-sensitive potassium (KATP) channels are not involved in the rutin action in pancreatic islets. In conclusion, rutin diminish glycemia, potentiate insulin secretion in vivo and significantly stimulates Ca2+ uptake in rat pancreatic islets. A novel cellular mechanism of action of rutin in Ca2+ uptake on pancreatic β-cells was elucidated. Rutin modulates Ca2+ uptake in pancreatic islets by opening L-VDCCs, alter intracellular Ca2+, PLC and PKC signaling pathways, characterizing KATP channel-independent pathways. These findings highlight rutin, a dietary adjuvant, as a potential insulin secretagogue contributing to glucose homeostasis.