ArticleDiabetes2015
Antiaging Gene Klotho Attenuates Pancreatic β-Cell Apoptosis in Type 1 Diabetes.
Article in Diabetes, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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The trial behind it
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Who cites it
50 citing papers in PubMed, 86 citations in OpenAlex.
- Soluble Klotho Is Decreased in Children With Type 1 Diabetes and Correlated With Metabolic Control.Frontiers in endocrinology · 2021Trial
- Exerkine-Mediated Inter-Organ Crosstalk and Translational Perspectives in Metabolic Diseases.Current obesity reports · 2026Review
- DNMT inhibitor ameliorates hyperglycemia and renal inflammation partially via reversing hypermethylation-induced Klotho suppression in diabetic mice.Clinical epigenetics · 2026Article
- α-Klotho Supplementation Mitigates Cumulative Exercise-Induced Fatigue via Coordinated NRF2-Mediated Antioxidant Defense and AKT/GS-Driven Hepatic Glycogen Supercompensation in Mice.International journal of molecular sciences · 2025Article
- Reversing Neuronal Klotho Dysfunction-Mediated Diabetic Neuropathy Through 16:8 Intermittent Fasting.Molecular neurobiology · 2025Article
- A cohort study on the correlation between serum Klotho levels and all-cause mortality in American diabetic populations.Diabetology & metabolic syndrome · 2025Article
- Association between magnesium depletion score and Klotho levels among U.S. adults: Findings from NHANES 2007-2016.Heliyon · 2025Article
- Article
- α-Klotho prevents diabetic retinopathy by reversing the senescence of macrophages.Cell communication and signaling : CCS · 2024Article
- Review
- The Antidiabetic Potential of Probiotics: A Review.Nutrients · 2024Review
- The interaction between klotho protein and epigenetic alteration in diabetes and treatment options.Journal of diabetes and metabolic disorders · 2024Review
- TNFα Induces DNA and Histone Hypomethylation and Pulmonary Artery Smooth Muscle Cell Proliferation Partly via Excessive Superoxide Formation.Antioxidants (Basel, Switzerland) · 2024Article
- Relationship between serum fibroblast growth factor 19 and vascular endothelial growth factor and soluble klotho protein in type 1 diabetic children.BMC pediatrics · 2023Article
- Potential application of Klotho as a prognostic biomarker for patients with diabetic kidney disease: a meta-analysis of clinical studies.Therapeutic advances in chronic disease · 2023Article
- Aging impairs arterial compliance via Klotho-mediated downregulation of B-cell population and IgG levels.Cellular and molecular life sciences : CMLS · 2022Article
- In Vivo Cardiac-specific Expression of Adenylyl Cyclase 4 Gene Protects against Klotho Deficiency-induced Heart Failure.Translational research : the journal of laboratory and clinical medicine · 2022Article
- Adult Mouse Kidney Stem Cells Orchestrate the De Novo Assembly of a Nephron via Sirt2-Modulated Canonical Wnt/β-Catenin Signaling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Protective association of Klotho rs495392 gene polymorphism against hepatic steatosis in non-alcoholic fatty liver disease patients.Clinical and molecular hepatology · 2022Article
- Inflammation as A Precursor of Atherothrombosis, Diabetes and Early Vascular Aging.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Apoptosis is the major cause of death of insulin-producing β-cells in type 1 diabetes mellitus (T1DM). Klotho is a recently discovered antiaging gene. We found that the Klotho gene is expressed in pancreatic β-cells. Interestingly, halplodeficiency of Klotho (KL(+/-)) exacerbated streptozotocin (STZ)-induced diabetes (a model of T1DM), including hyperglycemia, glucose intolerance, diminished islet insulin storage, and increased apoptotic β-cells. Conversely, in vivo β-cell-specific expression of mouse Klotho gene (mKL) attenuated β-cell apoptosis and prevented STZ-induced diabetes. mKL promoted cell adhesion to collagen IV, increased FAK and Akt phosphorylation, and inhibited caspase 3 cleavage in cultured MIN6 β-cells. mKL abolished STZ- and TNFα-induced inhibition of FAK and Akt phosphorylation, caspase 3 cleavage, and β-cell apoptosis. These promoting effects of Klotho can be abolished by blocking integrin β1. Therefore, these cell-based studies indicated that Klotho protected β-cells by inhibiting β-cell apoptosis through activation of the integrin β1-FAK/Akt pathway, leading to inhibition of caspase 3 cleavage. In an autoimmune T1DM model (NOD), we showed that in vivo β-cell-specific expression of mKL improved glucose tolerance, attenuated β-cell apoptosis, enhanced insulin storage in β-cells, and increased plasma insulin levels. The beneficial effect of Klotho gene delivery is likely due to attenuation of T-cell infiltration in pancreatic islets in NOD mice. Overall, our results demonstrate for the first time that Klotho protected β-cells in T1DM via attenuating apoptosis.
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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.