Saccharin Stimulates Insulin Secretion Dependent on Sweet Taste Receptor-Induced Activation of PLC Signaling Axis.

Joan Serrano,Mangala M. Soundarapandian,George A. Kyriazis,Ian S. Brown,Nishita N. Meshram,Carter Mason,Björn Tyrberg,Kathleen R. Smith

doi:10.3390/biomedicines10010120

Abstract

Background: Saccharin is a common artificial sweetener and a bona fide ligand for sweet taste receptors (STR). STR can regulate insulin secretion in beta cells, so we investigated whether saccharin can stimulate insulin secretion dependent on STR and the activation of phospholipase C (PLC) signaling. Methods: We performed in vivo and in vitro approaches in mice and cells with loss-of-function of STR signaling and specifically assessed the involvement of a PLC signaling cascade using real-time biosensors and calcium imaging. Results: We found that the ingestion of a physiological amount of saccharin can potentiate insulin secretion dependent on STR. Similar to natural sweeteners, saccharin triggers the activation of the PLC signaling cascade, leading to calcium influx and the vesicular exocytosis of insulin. The effects of saccharin also partially require transient receptor potential cation channel M5 (TRPM5) activity. Conclusions: Saccharin ingestion may transiently potentiate insulin secretion through the activation of the canonical STR signaling pathway. These physiological effects provide a framework for understanding the potential health impact of saccharin use and the contribution of STR in peripheral tissues.

Highlights

Published: 6 January 2022Artificial sweeteners (AS) are food additives that enhance sweet flavor without an extra energy burden
Using genetic and pharmacological approaches, we previously showed that fructose potentiates insulin secretion dependent on sweet taste receptors (STR) and the activation of a phospholipase C (PLC) signaling cascade [9]
Evidence for the expression of STR in isolated islets or beta‐cell lines is limited to RT‐

Summary

Introduction

Published: 6 January 2022Artificial sweeteners (AS) are food additives that enhance sweet flavor without an extra energy burden. Saccharin supplementation did not induce glucose intolerance in healthy overweight or obese individuals [4], nor did it change fasting glucose and insulin in patients with type 2 diabetes [5] These findings do not preclude possible effects of saccharin use, but understanding whether and how acute saccharin ingestion triggers the physiological process may be imperative for shedding light on its chronic effects. Conclusions: Saccharin ingestion may transiently potentiate insulin secretion through the activation of the canonical STR signaling pathway. These physiological effects provide a framework for understanding the potential health impact of saccharin use and the contribution of STR in peripheral tissues

Methods

Results

Conclusion