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PNAS 109 (8): 524-532

Copyright © 2012 by the National Academy of Sciences.

PNAS Plus


PNAS PLUS / BIOLOGICAL SCIENCES / PHYSIOLOGY

Sweet taste receptor signaling in beta cells mediates fructose-induced potentiation of glucose-stimulated insulin secretion

George A. Kyriazis, Mangala M. Soundarapandian, and Björn Tyrberg1

Metabolic Signaling and Disease, Diabetes and Obesity Research Center, Sanford–Burnham Medical Research Institute, Orlando, FL 32827

1To whom correspondence should be addressed. E-mail: btyrberg{at}sanfordburnham.org.

Abstract: Postprandial insulin release is regulated by glucose, but other circulating nutrients may target beta cells and potentiate glucose-stimulated insulin secretion via distinct signaling pathways. We demonstrate that fructose activates sweet taste receptors (TRs) on beta cells and synergizes with glucose to amplify insulin release in human and mouse islets. Genetic ablation of the sweet TR protein T1R2 obliterates fructose-induced insulin release and its potentiating effects on glucose-stimulated insulin secretion in vitro and in vivo. TR signaling in beta cells is triggered, at least in part, in parallel with the glucose metabolic pathway and leads to increases in intracellular calcium that are dependent on the activation of phospholipase C (PLC) and transient receptor potential cation channel, subfamily M, member 5 (TRPM5). Our results unveil a pathway for the regulation of insulin release by postprandial nutrients that involves beta cell sweet TR signaling.

Key Words: saccharin • G-protein coupled receptor • T1R3 • glucagon-like peptide-1 • MIN6


 

The authors declare no conflict of interest.

This article is a PNAS Direct Submission.

See full research article on page E524 of www.pnas.org.

Cite this Author Summary as: PNAS 10.1073/pnas.1115183109.

Find additional patient-related information at:

Fructose boosts insulin production by beta cells

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