ArticleNature communications2022
Regulation of age-associated insulin resistance by MT1-MMP-mediated cleavage of insulin receptor.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 45 citations in OpenAlex.
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- Single-cell and spatial omics in liver identify cell-cell communication regulators in aging and insulin resistance.Metabolism: clinical and experimental · 2026Article
- Rapamycin Reverses the Hepatic Response to Diet-Induced Metabolic Stress That Is Amplified by Aging.Aging cell · 2026Article
- Proteomics of aging: biomarkers for physiological systems and diseases.Frontiers in aging · 2026Review
- Severe Insulin Resistance: Diagnosis and Management.Current diabetes reviews · 2026Review
- The protein phosphatase 6 subunit SAPS3 modulates lifespan by regulating metabolism.Science advances · 2025Article
- MT1-MMP inhibition rejuvenates ageing brain and rescues cognitive deficits in obesity.Cell discovery · 2025Article
- Report of the 5th International Symposium on Frontiers in Molecular Science (ISFMS 2025).International journal of molecular sciences · 2025Article
- Metabolic Regulation of Cardiovascular Aging.Current cardiology reports · 2025Review
- Regulation and function of insulin and insulin-like growth factor receptor signalling.Nature reviews. Molecular cell biology · 2025Review
- Obesity accelerates cardiovascular ageing.European heart journal · 2025Review
- Soluble CD13 is a potential mediator of neutrophil-induced thrombogenic inflammation in SARS-CoV-2 infection.JCI insight · 2025Article
- Regulation of the terminal complement cascade in adipose tissue for control of its volume, cellularity, and fibrosis.Obesity (Silver Spring, Md.) · 2025Review
- Allosteric targeted drug delivery for enhanced blood-brain barrier penetration via mimicking transmembrane domain interactions.Nature communications · 2025Article
- Potential Impact of Choline Alphoscerate on Depressive Symptoms in Association with Insulin Resistance in Elderly Patients with Type 2 Diabetes.Journal of clinical medicine · 2025Article
- Interplay Between Insulin Resistance and Immune Dysregulation in Type 2 Diabetes Mellitus: Implications for Therapeutic Interventions.ImmunoTargets and therapy · 2025Review
- Correlation between lipid accumulation product and epigenetic age acceleration in American adults: a cross-sectional analysis using NHANES data.European journal of medical research · 2024Article
- Melatonin Ameliorates Abnormal Sleep-Wake Behavior via Facilitating Lipid Metabolism in a Zebrafish Model of Parkinson's Disease.Neuroscience bulletin · 2024Article
- Hepatocyte MMP14 mediates liver and inter-organ inflammatory responses to diet-induced liver injury.PNAS nexus · 2024Article
Corrections and comments
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Authors and funding
22 authors at 4 institutions in 4 countries.
Funding
Abstract
Insulin sensitivity progressively declines with age. Currently, the mechanism underlying age-associated insulin resistance remains unknown. Here, we identify membrane-bound matrix metalloproteinase 14 (MT1-MMP/MMP14) as a central regulator of insulin sensitivity during ageing. Ageing promotes MMP14 activation in insulin-sensitive tissues, which cleaves Insulin Receptor to suppress insulin signaling. MT1-MMP inhibition restores Insulin Receptor expression, improving insulin sensitivity in aged mice. The cleavage of Insulin Receptor by MT1-MMP also contributes to obesity-induced insulin resistance and inhibition of MT1-MMP activities normalizes metabolic dysfunctions in diabetic mouse models. Conversely, overexpression of MT1-MMP in the liver reduces the level of Insulin Receptor, impairing hepatic insulin sensitivity in young mice. The soluble Insulin Receptor and circulating MT1-MMP are positively correlated in plasma from aged human subjects and non-human primates. Our findings provide mechanistic insights into regulation of insulin sensitivity during physiological ageing and highlight MT1-MMP as a promising target for therapeutic avenue against diabetes.
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