Sweet taste receptor signaling in beta cells mediates fructose-induced potentiation of glucose-stimulated insulin secretion.
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.
Metabolic Signaling and Disease, Diabetes and Obesity Research Center, Sanford-Burnham Medical Research Institute, Orlando, FL 32827, USA.
George A
GA
Kyriazis
Mangala M
MM
Soundarapandian
Björn
B
Tyrberg
D000818:Animals; D002118:Calcium / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005632:Fructose / Q000494:pharmacology*; D017353:Gene Deletion; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D019518:Postprandial Period / Q000187:drug effects; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D050053:TRPM Cation Channels / Q000378:metabolism; D013649:Taste / Q000187:drug effects*; D010738:Type C Phospholipases / Q000378:metabolism
D007328:Insulin; D043562:Receptors, G-Protein-Coupled; D050053:TRPM Cation Channels; C498617:Trpm5 protein, mouse; C431926:taste receptors, type 1; D005632:Fructose; D010738:Type C Phospholipases; D005947:Glucose; D002118:Calcium