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

• Published in: Biomedicines Vol. 10; no. 1; p. 120
• Main Authors: Serrano, Joan, Meshram, Nishita N, Soundarapandian, Mangala M, Smith, Kathleen R, Mason, Carter, Brown, Ian S, Tyrberg, Björn, Kyriazis, George A
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.01.2022; MDPI
• Subjects: Artificial sweeteners; Beta cells; Biosensors; Calcium; Calcium imaging; Calcium influx; Cell culture; Clinical Medicine; Cloning; Exocytosis; Experiments; Glucagon; Glucose; Glucose tolerance; Insulin; Insulin secretion; Klinisk medicin; Laboratory animals; Ligands; Munc13-1; Phospholipase C; Physiology; PLC; Saccharin; Secretion; Signal transduction; Sweet taste; Sweet taste receptors; Sweeteners; T1R2; T1r2-Cre; T1R3; Taste receptors; Tdtomato; Transient receptor potential proteins; TRPM5; United States > US; calcium; PLC; sweet taste receptors; Tdtomato; insulin secretion; Munc13-1; artificial sweeteners; T1r2-Cre; T1R3; T1R2; TRPM5; glucose tolerance; beta cells; saccharin
• ISSN: 2227-9059; 2227-9059
• DOI: 10.3390/biomedicines10010120

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. 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. 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. 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.