ArticleDiabetologia2020
Plasma cathepsin D activity is negatively associated with hepatic insulin sensitivity in overweight and obese humans.
Article in Diabetologia, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 37 citations in OpenAlex.
- Proteomic mechanistic profile of patients with diabetes at risk of developing heart failure: insights from the HOMAGE trial.Cardiovascular diabetology · 2021Trial
- Cathepsin D-driven IL2RG-JAK2 signal hijacking disrupts hepatic insulin action: mechanism-grounded proof that targeting cathepsin D prevents prediabetes.International journal of obesity (2005) · 2026Article
- Faecal metaproteomics analysis reveals a high cardiovascular risk profile across healthy individuals and heart failure patients.Gut microbes · 2025Article
- Circulating Cathepsin D Exacerbates Injury-Induced Brain Damage by Promoting Neutrophil Infiltration Into the Brain.Journal of the American Heart Association · 2025Article
- Pathophysiological hallmarks in type 2 diabetes heterogeneity (review).Diabetology international · 2025Review
- Circulatory cathepsin K as biomarkers in older adults with sarcopenia: a case-control study.Frontiers in medicine · 2025Article
- Asparagine-related biomarkers and regulatory mechanisms in type 2 diabetes mellitus.Frontiers in molecular biosciences · 2025Article
- The Effect of Vitamin D3 Injection Combined With High-Intensity Interval Training on Excessive Autophagy in the Heart Tissue of Type 2 Diabetes-Induced Rats: An Analysis of the mTOR-Beclin-1-Fyco-1-Cathepsin D Pathway.Cardiovascular therapeutics · 2025Article
- The multifaceted roles of cathepsins in immune and inflammatory responses: implications for cancer therapy, autoimmune diseases, and infectious diseases.Biomarker research · 2024Review
- Hyperglycemia induced cathepsin L maturation linked to diabetic comorbidities and COVID-19 mortality.eLife · 2024Article
- Targeted Proteomics Reveals Functional Targets for Early Diabetes Susceptibility in Young Adults.Circulation. Genomic and precision medicine · 2024Article
- Hallmarks of the metabolic secretome.Trends in endocrinology and metabolism: TEM · 2024Review
- Multi-tissue epigenetic analysis identifies distinct associations underlying insulin resistance and Alzheimer's disease at CPT1A locus.Clinical epigenetics · 2023Article
- All Roads Lead to Cathepsins: The Role of Cathepsins in Non-Alcoholic Steatohepatitis-Induced Hepatocellular Carcinoma.Biomedicines · 2022Review
- Inhibition of Extracellular Cathepsin D Reduces Hepatic Lipid Accumulation and Leads to Mild Changes in Inflammationin NASH Mice.Frontiers in immunology · 2021Article
- Review
- Plasma Cathepsin D Activity Rather Than Levels Correlates With Metabolic Parameters of Type 2 Diabetes in Male Individuals.Frontiers in endocrinology · 2020Article
- Cathepsin gene expression in abdominal subcutaneous adipose tissue of obese/overweight humans.Adipocyte · 2020Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisInsulin resistance in skeletal muscle and liver plays a major role in the pathophysiology of type 2 diabetes. The hyperinsulinaemic-euglycaemic clamp is considered the gold standard for assessing peripheral and hepatic insulin sensitivity, yet it is a costly and labour-intensive procedure. Therefore, easy-to-measure, cost-effective approaches to determine insulin sensitivity are needed to enable organ-specific interventions. Recently, evidence emerged that plasma cathepsin D (CTSD) is associated with insulin sensitivity and hepatic inflammation. Here, we aimed to investigate whether plasma CTSD is associated with hepatic and/or peripheral insulin sensitivity in humans.
methodsAs part of two large clinical trials (one designed to investigate the effects of antibiotics, and the other to investigate polyphenol supplementation, on insulin sensitivity), 94 overweight and obese adults (BMI 25-35 kg/m
resultsPlasma CTSD levels were positively associated with the proinflammatory cytokines IL-8 and TNF-α (IL-8: standardised β = 0.495, p < 0.001; TNF-α: standardised β = 0.264, p = 0.012). Plasma CTSD activity was negatively associated with hepatic insulin sensitivity (standardised β = -0.206, p = 0.043), independent of age, sex, BMI and waist circumference, but it was not associated with peripheral insulin sensitivity. However, plasma IL-8 and TNF-α were not significantly correlated with hepatic insulin sensitivity. CONCLUSIONS/
interpretationWe demonstrate that plasma CTSD activity, but not systemic inflammation, is inversely related to hepatic insulin sensitivity, suggesting that plasma CTSD activity may be used as a non-invasive marker for hepatic insulin sensitivity in humans.
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