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<p>Pancreatic β-cell function defects are responsible for the pathology of both type 1 and type 2 diabetes. The sensitivity of mTOR Complex 1 (mTORC1) to insulin and nutrients suggests its importance in β-cell function. To assess the effect of mTOR signaling in mouse β-cells, we specifically deleted the mTOR gene in this cellular compartment. These mice display glucose intolerance and do not secrete insulin in response to a glucose challenge. Similarly, depletion of mTOR via siRNA in INS-1 cells demonstrated that the kinase is necessary for glucose-stimulated insulin secretion (GSIS). The effects of mTOR on GSIS were dependent on mTORC1, not mTORC2, and resulted in a selective reduction of NeuroD1 expression, with no impact on PDX1. These findings on NeuroD1 expression were also observed in the islets of diabetic patients. Overall, mTOR signaling regulates insulin secretion and production in β-cells through mTORC1 and NeuroD1.</p>

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Mammalian target of rapamycin is required for insulin secretion in pancreatic β-cells via NeuroD1 in vitro and in vivo

  • 期刊论文

  • 发表日期：

    2026年6月22日

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  • Jongsun Park,
  • Jisoo Park,
  • Hyunji Lee,
  • Jandee Lee,
  • Young Suk Jo,
  • David D’Alessio,
  • Christopher B. Newgard,
  • George Thomas,
  • Sara C. Kozma

摘要

Pancreatic β-cell function defects are responsible for the pathology of both type 1 and type 2 diabetes. The sensitivity of mTOR Complex 1 (mTORC1) to insulin and nutrients suggests its importance in β-cell function. To assess the effect of mTOR signaling in mouse β-cells, we specifically deleted the mTOR gene in this cellular compartment. These mice display glucose intolerance and do not secrete insulin in response to a glucose challenge. Similarly, depletion of mTOR via siRNA in INS-1 cells demonstrated that the kinase is necessary for glucose-stimulated insulin secretion (GSIS). The effects of mTOR on GSIS were dependent on mTORC1, not mTORC2, and resulted in a selective reduction of NeuroD1 expression, with no impact on PDX1. These findings on NeuroD1 expression were also observed in the islets of diabetic patients. Overall, mTOR signaling regulates insulin secretion and production in β-cells through mTORC1 and NeuroD1.