Suppression of ITPK1 and IPMK activities impairs mTORC1 signaling due to accelerated signal termination and prevents pancreatic β-cell metabolic adaptation to excess glucose

Suppressing IPMK or ITPK1 in pancreatic β-cells reduces IP5 and delays mTORC1-dependent metabolic acceleration under excess glucose, linked to faster mTORC1 signal termination.

• Why it matters: mTORC1 integrates nutrient cues, but direct metabolite control is unclear; defining how inositol phosphates tune mTORC1 persistence could enable metabolic regulation.
• What they did: In HEK293 and pancreatic β-cells, the authors suppressed or acutely inhibited IPMK (and/or ITPK1) to lower IP5, then measured basal/insulin- and glucose-stimulated mTORC1 signaling and signal termination.
• The result: IP5 depletion did not block PI3K/Akt activation or insulin/glucose-driven mTORC1 activation, but accelerated mTORC1 signal termination and delayed β-cell metabolic adaptation to excess glucose.

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