Sucralose activates an ERK1/2-ribosomal protein S6 signaling axis.
The sweetener sucralose can signal through its GPCR receptor to induce insulin secretion from pancreatic β cells, but the downstream signaling pathways involved are not well-understood. Here we measure responses to sucralose, glucagon-like peptide 1, and amino acids in MIN6 β cells. Our data suggest a signaling axis, whereby sucralose induces calcium and cAMP, activation of ERK1/2, and site-specific phosphorylation of ribosomal protein S6. Interestingly, sucralose acted independently of mTORC1 or ribosomal S6 kinase (RSK). These results suggest that sweeteners like sucralose can influence β-cell responses to secretagogues like glucose through metabolic as well as GPCR-mediated pathways. Future investigation of novel sweet taste receptor signaling pathways in β cells will have implications for diabetes and other emergent fields involving these receptors.
Department of Pharmacology UT Southwestern Medical Center Dallas TX USA; Present address: Stem Synergy Therapeutics Nashville TN USA.
Marcy L
ML
Guerra
Department of Pharmacology UT Southwestern Medical Center Dallas TX USA.
Michael A
0000-0002-8349-9470
MA
Kalwat
Department of Pharmacology UT Southwestern Medical Center Dallas TX USA.
Kathleen
K
McGlynn
Department of Pharmacology UT Southwestern Medical Center Dallas TX USA.
Melanie H
MH
Cobb
insulin secretion; pancreatic islet beta cells; sucralose; sweet taste receptor