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

Abstract

Postprandial insulin release is regulated by glucose, but other circulating nutrients may target beta cells and potentiate glucosestimulated 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.saccharin | G-protein coupled receptor | T1R3 | glucagon-like peptide-1 | MIN6

Expression of the glucose-sensing receptor T1R3 in pancreatic islet: changes in the expression levels in various nutritional and metabolic states

“…We then measured the expression levels of mRNA for T1R2 and T1R3 by quantitative RT-PCR. In agreement with a previous report [17], the expression level of T1R2 was quite low compared to that of T1R3. In fact, the expression level of T1R2 was less than 1% of that of T1R3 (Fig.…”

“…1C). These results confirm the previous report by Kyriazis et al [17]. In agreement with the expression of mRNA, immunoreactive T1R2 was not detected in mouse pancreatic islets.…”

Glucose promotes its own metabolism by acting on the cell-surface glucose-sensing receptor T1R3

“…Interaction of the glucose-sensing receptor signals and metabolic signals may be a basis for the efficient glucose sensing mechanism of β-cells as a fuel sensor. In β-cells, the sweet taste-sensing receptor senses fructose as well [20]. Pancreatic β-cells thus express cell-surface sugar-sensors to regulate insulin secretion.…”

Hepatic lipid accumulation: cause and consequence of dysregulated glucoregulatory hormones

“…In addition to providing the carbons necessary for fatty acid synthesis, fructose also induces signaling pathways that encourage lipogenesis. Fructose potentiates glucose-stimulated insulin secretion (Kyriazis et al 2012), increasing insulin-mediated SREBP1c signaling in the hepatocyte. Fructose also increases SREBP1c expression and activity independent of insulin.…”