ArticleCellular and molecular life sciences : CMLS2013
Vaspin inhibits kallikrein 7 by serpin mechanism.
Article in Cellular and molecular life sciences : CMLS, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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Who cites it
73 citing papers in PubMed, 162 citations in OpenAlex.
- Biomarkers of Cardiovascular Stress: A Historical Review.Journal of cardiovascular development and disease · 2026Review
- Novel Adipokines in Critical Illness and Sepsis: Chemerin, Vaspin, and Omentin-1: A Comprehensive Evidence-Based Review.Biomedicines · 2026Review
- The Serpin Superfamily in Adipose Tissue Remodeling: Molecular Drivers of Immune-Metabolic Crosstalk and Insulin Sensitivity.Biology · 2026Review
- Vaspin identified as a DNA-binding serpin with functional consequences for protease inhibition.The FEBS journal · 2026Article
- Inverse association of circulating kallikrein-related peptidase 7 with renal function and mortality risk in patients with chronic kidney disease.Frontiers in endocrinology · 2026Article
- SERPINA12 in skin: molecular mechanisms and roles in adipocytes, psoriasis, and palmoplantar keratoderma.Frontiers in immunology · 2026Review
- Drug Discovery Strategies for Kallikrein-Related Peptidases.International journal of molecular sciences · 2025Review
- Inhibition of adipocyte lipolysis by vaspin impairs thermoregulation in vivo.Nature communications · 2025Article
- From Adipose Tissue to Endothelial Cells-Pleiotropic Role of Vaspin in Pathogenesis of Metabolic and Cardiovascular Diseases.Biomedicines · 2025Review
- Kinin receptors in adipose tissue: drivers of inflammation and metabolic dysfunction in obesity.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- Effect of adipokines on bone marrow mesenchymal stem cell function.World journal of stem cells · 2025Review
- Omega-3 Fatty Acids and Exercise in Obesity Management: Independent and Synergistic Benefits in Metabolism and Knowledge Gaps.Biology · 2025Review
- High-throughput amino acid-level characterization of the interactions of plasminogen activator inhibitor-1 with variably divergent proteases.Protein science : a publication of the Protein Society · 2025Article
- The roles of serine protease inhibitors in dermatoses.Frontiers in genetics · 2025Review
- Role of human Kallistatin in glucose and energy homeostasis in mice.Molecular metabolism · 2024Article
- Adipose Signals Regulating Distal Organ Health and Disease.Diabetes · 2024Review
- Regulation of epidermal barrier function and pathogenesis of psoriasis by serine protease inhibitors.Frontiers in immunology · 2024Review
- Parasitoid Serpins Evolve Novel Functions to Manipulate Host Homeostasis.Molecular biology and evolution · 2023Article
- Serendipitous Discovery of T Cell-Produced KLK1b22 as a Regulator of Systemic Metabolism.ImmunoHorizons · 2023Article
- Adipokines as Clinically Relevant Therapeutic Targets in Obesity.Biomedicines · 2023Review
13 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The molecular target of the adipokine vaspin (visceral adipose tissue-derived serpin; serpinA12) and its mode of action are unknown. Here, we provide the vaspin crystal structure and identify human kallikrein 7 (hK7) as a first protease target of vaspin inhibited by classical serpin mechanism with high specificity in vitro. We detect vaspin-hK7 complexes in human plasma and find co-expression of both proteins in murine pancreatic β-cells. We further demonstrate that hK7 cleaves human insulin in the A- and B-chain. Vaspin treatment of isolated pancreatic islets leads to increased insulin concentration in the media upon glucose stimulation without influencing insulin secretion. By application of vaspin and generated inactive mutants, we find the significantly improved glucose tolerance in C57BL/6NTac and db/db mice treated with recombinant vaspin fully dependent on the vaspin serpin activity and not related to vaspin-mediated changes in insulin sensitivity as determined by euglycemic-hyperinsulinemic clamp studies. Improved glucose metabolism could be mediated by increased insulin plasma concentrations 150 min after a glucose challenge in db/db mice, supporting the hypothesis that vaspin may inhibit insulin degradation by hK7 in the circulation. In conclusion, we demonstrate the inhibitory serpin nature and the first protease target of the adipose tissue-derived serpin vaspin, and our findings suggest hK7 inhibition by vaspin as an underlying physiological mechanism for its compensatory actions on obesity-induced insulin resistance.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.