Acute Insulin Releasing Effect of Hesperidin and Its Nano Delivery Systems in Pancreatic Islets

Abstract

Background: Hesperidin, a flavone glycoside, has been shown to exhibit anti-diabetic effects; however, its direct insulin secretory effect still needs to be explored. Additionally, it is poorly absorbed by intestine due to either enzymatic degradation in the stomach or its offsite effects. Purpose: Here, we investigated the possible insulinotropic mechanism(s) of hesperidin and its nano-carrier. Method: Hesperidin and its nano-formulations were co-incubated with mice islets in the presence and absence of agonists/antagonists. The insulin was measured using insulin ELISA kits. Results : Hesperidin, exerted insulin secretory effect only at stimulatory glucose concentrations as compared with glimepiride. We observed partial inhibition in hesperidin-induced insulin secretion using diazoxide, a K-ATP channel opener; whereas, complete inhibition by verapamil, a Ca2+ channel blocker. Hesperidin amplified glucose-induced insulin secretion in glimepiride-treated and depolarized islets. Hesperidin showed additive effect in FSK-induced insulin secretion and no additive effect in IBMX-induced insulin secretion. Hesperidin-induced insulin secretion was significantly inhibited by H-89, a PKA inhibitor, and U0126, a MEK kinase inhibitor, respectively. Additionally, gum acacia stabilized/reduced green silver nanoparticle of hesperidin significantly enhanced the insulin secretory effects. Conclusion : Hesperidin amplifies insulin secretion through PKA and MEK kinase signaling pathway coupled with glucose for insulin secretion. Funding Information: This work was supported by a Grant#8544 from the Higher Education Commission (HEC), Pakistan to Md. Hafizur Rahman. Declaration of Interests: We wish to declare that there are no known conflicts of interest with the research reported that could have influence the outcome. Ethics Approval Statement: All animal experiments were carried out with prior approval from the Animal Use Committee of the International Center for Chemical and Biological Sciences (ICCBS), University of Karachi, Pakistan (Protocol number: 2015-0020).