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Updated: Jan 15, 2026

High-resolution Respirometry to Measure Mitochondrial Function of Intact Beta Cells in the Presence of Natural Compounds

High-resolution Respirometry to Measure Mitochondrial Function of Intact Beta Cells in the Presence of Natural Compounds

Published on: January 23, 2018

mTORC1によるPDX1のS61リン酸化は、栄養シグナル伝達とβ細胞機能および代謝疾患を関連付ける

Jialin Fan¹, Xin Zhang¹, Jinling Zhang¹

¹Rutgers Cancer Institute, Rutgers, the State University of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08901, USA; Department of Pharmacology, Robert Wood Johnson Medical School, Rutgers, the State University of New Jersey, 675 Hoes Lane, Piscataway, NJ 08854, USA.

|January 13, 2026

Abstract:

PDX1 is a key transcription factor regulating insulin expression in response to glucose. Our previous work showed that PDX1 is also stimulated by amino acids (aa). Here, we demonstrate that PDX1 broadly mediates aa-regulated transcriptional programs in β cells, especially those controlling β cell proliferation and function. Mechanistically, mTORC1 phosphorylates PDX1 at serine 61 (S61), enhancing its protein stability and transcriptional activity. A certain monogenic diabetes mutation disrupts this phosphorylation and impairs PDX1 function. To investigate its physiological role, we generated mice carrying S61A and S61E mutations, mimicking unphosphorylated and phosphorylated states. S61 phosphorylation promoted insulin expression and β cell proliferation, leading to Western diet-induced hyperinsulinemia, obesity, and hepatic steatosis. These findings reveal the central role of aa-mTORC1-PDX1 signaling in coordinating β cell proliferation and function under both physiological and pathological conditions.

キーワード:

代謝分子生物学 MODY アミノ酸糖尿病グルコース高インスリン血症インスリン肝 steatosis mTOR 栄養素肥満 pdx1 β細胞

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Isolation of Primary Mouse Hepatocytes for Nascent Protein Synthesis Analysis by Non-radioactive L-azidohomoalanine Labeling Method

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