Pyruvate kinase modulates the link between β‐cell fructose metabolism and insulin secretion DOI Creative Commons
Naoya Murao,

Risa Morikawa,

Yusuke Seino

и другие.

The FASEB Journal, Год журнала: 2025, Номер 39(7)

Опубликована: Март 28, 2025

Abstract The intricate link between glucose metabolism, ATP production, and glucose‐stimulated insulin secretion (GIIS) in pancreatic β‐cells has been well established. However, the effects of other digestible monosaccharides on this mechanism remain unclear. This study examined interaction intracellular fructose metabolism GIIS using MIN6‐K8 β‐cell lines mouse islets. Fructose at millimolar concentrations potentiated presence stimulatory levels (8.8 mM) glucose. potentiation was dependent sweet taste receptor‐activated phospholipase Cβ2 (PLCβ2) signaling. Concurrently, metabolic tracing 13 C‐labeled conjunction with biochemical analyses demonstrated that blunted glucose‐induced increase ATP/ADP ratio. Mechanistically, is substantially converted to 1‐phosphate (F1P) expense ATP. F1P directly inhibited PKM2 (pyruvate kinase M2), thereby reducing later glycolytic flux used for production. Remarkably, F1P‐mediated inhibition counteracted by TEPP‐46, a small‐molecule activator. TEPP‐46 restored ratio, leading enhancement fructose‐potentiated cells, normal islets, fructose‐unresponsive diabetic These findings reveal an antagonistic interplay β‐cells, highlighting as crucial regulator broadening our understanding relationship fuel secretion.

Язык: Английский

Pyruvate kinase modulates the link between β‐cell fructose metabolism and insulin secretion DOI Creative Commons
Naoya Murao,

Risa Morikawa,

Yusuke Seino

и другие.

The FASEB Journal, Год журнала: 2025, Номер 39(7)

Опубликована: Март 28, 2025

Abstract The intricate link between glucose metabolism, ATP production, and glucose‐stimulated insulin secretion (GIIS) in pancreatic β‐cells has been well established. However, the effects of other digestible monosaccharides on this mechanism remain unclear. This study examined interaction intracellular fructose metabolism GIIS using MIN6‐K8 β‐cell lines mouse islets. Fructose at millimolar concentrations potentiated presence stimulatory levels (8.8 mM) glucose. potentiation was dependent sweet taste receptor‐activated phospholipase Cβ2 (PLCβ2) signaling. Concurrently, metabolic tracing 13 C‐labeled conjunction with biochemical analyses demonstrated that blunted glucose‐induced increase ATP/ADP ratio. Mechanistically, is substantially converted to 1‐phosphate (F1P) expense ATP. F1P directly inhibited PKM2 (pyruvate kinase M2), thereby reducing later glycolytic flux used for production. Remarkably, F1P‐mediated inhibition counteracted by TEPP‐46, a small‐molecule activator. TEPP‐46 restored ratio, leading enhancement fructose‐potentiated cells, normal islets, fructose‐unresponsive diabetic These findings reveal an antagonistic interplay β‐cells, highlighting as crucial regulator broadening our understanding relationship fuel secretion.

Язык: Английский

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