ArticleEndocrinology2015
The protective effect of FGF21 on diabetes-induced male germ cell apoptosis is associated with up-regulated testicular AKT and AMPK/Sirt1/PGC-1α signaling.
Article in Endocrinology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 56 citations in OpenAlex.
- The Liver-Testis Axis: Molecular Mechanisms and Clinical Implications.International journal of molecular sciences · 2026Review
- Functions of FGF21 and its role in cardiac hypertrophy.Journal of advanced research · 2026Review
- SIRT1 mediated autophagy enhancement by Lactobacillus fermentum derived oligosaccharides accelerates wound healing in biofilm associated infection.Scientific reports · 2025Article
- Research progress on the role of FGF21 in insulin resistance.Frontiers in endocrinology · 2025Review
- Effects of diabetes-induced hyperglycemia on epigenetic modifications and DNA packaging and methylation during spermatogenesis; A narrative review.Iranian journal of basic medical sciences · 2024Review
- Effect of Oleanolic acid administration on hepatic AMPK, SIRT-1, IL-6 and NF-κB levels in experimental diabetes.Journal of diabetes and metabolic disorders · 2023Article
- PFOS-elicited metabolic perturbation in liver and fatty acid metabolites in testis of adult mice.Frontiers in endocrinology · 2023Article
- Type 2 Diabetes Induces a Pro-Oxidative Environment in Rat Epididymis by Disrupting SIRT1/PGC-1α/SIRT3 Pathway.International journal of molecular sciences · 2022Article
- The PI3K/AKT signaling pathway: How does it regulate development of Sertoli cells and spermatogenic cells?Histology and histopathology · 2022Review
- Rifaximin Protects against Malathion-Induced Rat Testicular Toxicity: A Possible Clue on Modulating Gut Microbiome and Inhibition of Oxidative Stress by Mitophagy.Molecules (Basel, Switzerland) · 2022Article
- Epigallocatechin-3-gallate ameliorates hepatic damages by relieve FGF21 resistance and promotion of FGF21-AMPK pathway in mice fed a high fat diet.Diabetology & metabolic syndrome · 2022Article
- Mechanistic insights into the role of FOXO in diabetic retinopathy.American journal of translational research · 2022Review
- Histone Deacetylases as Modulators of the Crosstalk Between Skeletal Muscle and Other Organs.Frontiers in physiology · 2022Review
- Evaluation of testicular glycogen storage, FGF21 and LDH expression and physiological parameters of sperm in hyperglycemic rats treated with hydroalcoholic extract of Securigera Securidaca seeds, and Glibenclamide.Reproductive biology and endocrinology : RB&E · 2021Article
- Therapeutic Effects of Fibroblast Growth Factor-21 on Diabetic Nephropathy and the Possible Mechanism in Type 1 Diabetes Mellitus Mice.Diabetes & metabolism journal · 2020Article
- Fibroblast Growth Factor 21 Attenuates Diabetes-Induced Renal Fibrosis by Negatively Regulating TGF-β-p53-Smad2/3-Mediated Epithelial-to-Mesenchymal Transition via Activation of AKT.Diabetes & metabolism journal · 2020Article
- The Role of Akt2 in the Protective Effect of Fenofibrate against Diabetic Nephropathy.International journal of biological sciences · 2020Article
- Article
- Ghrelin attenuates oxidative stress and neuronal apoptosis via GHSR-1α/AMPK/Sirt1/PGC-1α/UCP2 pathway in a rat model of neonatal HIE.Free radical biology & medicine · 2019Article
- Aerobic Exercise Training Decreases Hepatic Asprosin in Diabetic Rats.Journal of clinical medicine · 2019Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Fibroblast growth factor 21 (FGF21) is a metabolic regulator that is required for normal spermatogenesis and protects against diabetes-induced germ cell apoptosis. Here, we tried to define whether diabetes-induced germ cell apoptosis that is predominantly due to increased oxidative stress was associated with impaired glucose and fatty acid metabolism, by examining the effects of Fgf21 gene knockout (FGF21-KO) or FGF21 treatment on the glucose and fatty acid metabolic pathways in streptozotocin-induced diabetic mice. Western blottings revealed that protein kinase B (AKT)-mediated glucose signaling was down-regulated in diabetic testes and further decreased in FGF21-KO diabetic group both 10 days and 2 months after diabetes onset, reflected by reduced glycogen synthase (GS) kinase (GSK)-3β phosphorylation and increased GS phosphorylation. Deletion of the Fgf21 gene also inactivated fatty acid metabolism-related factors, AMP-activated protein kinase (AMPK), sirtuin 1 (Sirt1), and peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α), along with exacerbating diabetes-induced testicular oxidative stress and damage. Treatment with recombinant FGF21 partially prevented these diabetic effects. In FGF21-KO nondiabetic mice, testicular AMPK/Sirt1/PGC-1α signaling was down-regulated and AKT1 and murine double minute 2 were inactivated along with the increased p53 expression but not AKT2, GSK-3β, and GS. These results suggest that the role of FGF21 in maintaining spermatogenesis is associated with its activation of AKT1 and inhibition of p53. Deletion of the Fgf21gene significantly exacerbates diabetes-induced down-regulation of testicular AKT/GSK-3β/GS and AMPK/Sirt1/PGC-1α pathways and testicular oxidative stress and cell apoptosis.
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