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October 5, 2025Open Access

Metformin inhibits mitochondrial complex I in intestinal epithelium to promote glycemic control

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Authors

ZSZachary L. SeboRCRam Prosad ChakrabartyRGRogan A. Grant

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Overview

Observational analysis demonstrates complex I inhibition enhances glucose uptake in the intestines, suggesting a novel mechanism of glycemic control.

Key Points

  • Complex I inhibition by metformin lowers blood sugar levels, driving intestinal glucose uptake and lactate production.
  • Elevations in metabolites like GDF15 and lactate were observed in response to metformin's action in the intestine.
  • Assessment using human metabolomic data and mouse genetics reveals a shared mechanism among metformin and similar drugs.
  • This mechanism highlights therapeutic pathways for glucose regulation, warranting further investigation in clinical contexts.

Cite This Study

Sebo et al. (2025) studied this question.

synapsesocial.com/papers/68e24e60d6d66a53c24734b0https://doi.org/10.1101/2025.10.02.678294
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