Miro1 mediates skeletal muscle insulin resistance in type 2 diabetes

Abstract

Imbalanced skeletal muscle mitochondrial dynamics contribute to the onset and progression of type 2 diabetes (T2D) by mechanisms that remain incompletely understood. Here, we examined the role of Mitochondrial Rho GTPase 1 (Miro1), an outer mitochondrial membrane enzyme, in regulating skeletal muscle insulin action and glucose homeostasis in type 2 diabetes (T2D). In a cross-sectional clinical study, we show that Miro1 accumulates in the skeletal muscle of patients with obesity and T2D, which was further replicated in mouse models of T2D. This accumulation is explained by inadequate insulin-mediated interaction between AKT and Miro1 at the outer mitochondrial membrane. In a randomized controlled trial (NCT02977442), we show that exercise training relieves skeletal muscle Miro1 accumulation while improving insulin sensitivity in patients with T2D. Muscle-specific Miro1 deletion improves oxidative capacity and insulin sensitivity in mice and cells. Taken together, these data support a key regulatory role for skeletal muscle Miro1 in the pathophysiology of T2D. ClinicalTrials.gov Identifier: NCT02977442.

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Cite

BibTeX RIS

BibTeX

@article{heintz2026miro1,
  title = {{Miro1 mediates skeletal muscle insulin resistance in type 2 diabetes}},
  author = {Elizabeth C. Heintz and Wagner S. Dantas and Analisa L. Taylor and Elizabeth R. M. Zunica and Kathryn P. Belmont and Jackson M. Slone and Jacob T. Mey and Robbie Beyl and Bolormaa Vandanmagsar and Hailey A. Parry and Peter Ajayi and Brian Glancy and Christopher L. Axelrod and John P. Kirwan},
  journal = {Nature Communications},
  year = {2026},
  month = oct,
  doi = {10.1038/s41467-026-77278-6},
  url = {https://www.nature.com/articles/s41467-026-77278-6},
  note = {CC BY-NC-ND 4.0},
}

RIS

TY  - JOUR
TI  - Miro1 mediates skeletal muscle insulin resistance in type 2 diabetes
AU  - Elizabeth C. Heintz
AU  - Wagner S. Dantas
AU  - Analisa L. Taylor
AU  - Elizabeth R. M. Zunica
AU  - Kathryn P. Belmont
AU  - Jackson M. Slone
AU  - Jacob T. Mey
AU  - Robbie Beyl
AU  - Bolormaa Vandanmagsar
AU  - Hailey A. Parry
AU  - Peter Ajayi
AU  - Brian Glancy
AU  - Christopher L. Axelrod
AU  - John P. Kirwan
PY  - 2026
DA  - 2026/10/19
JO  - Nature Communications
DO  - 10.1038/s41467-026-77278-6
UR  - https://www.nature.com/articles/s41467-026-77278-6
AB  - Imbalanced skeletal muscle mitochondrial dynamics contribute to the onset and progression of type 2 diabetes (T2D) by mechanisms that remain incompletely understood. Here, we examined the role of Mitochondrial Rho GTPase 1 (Miro1), an outer mitochondrial membrane enzyme, in regulating skeletal muscle insulin action and glucose homeostasis in type 2 diabetes (T2D). In a cross-sectional clinical study, we show that Miro1 accumulates in the skeletal muscle of patients with obesity and T2D, which was further replicated in mouse models of T2D. This accumulation is explained by inadequate insulin-mediated interaction between AKT and Miro1 at the outer mitochondrial membrane. In a randomized controlled trial (NCT02977442), we show that exercise training relieves skeletal muscle Miro1 accumulation while improving insulin sensitivity in patients with T2D. Muscle-specific Miro1 deletion improves oxidative capacity and insulin sensitivity in mice and cells. Taken together, these data support a key regulatory role for skeletal muscle Miro1 in the pathophysiology of T2D. ClinicalTrials.gov Identifier: NCT02977442.
SN  - 2041-1723
ER  -

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