β-Klotho promotes glycolysis and glucose-stimulated insulin secretion via GP130

Geng, Leiluo; Liao, Boya; Jin, Libo; Yu, Jiasui; Zhao, Xiaoyu; Zhao, Yuntao; Zhong, Ling; Wang, Baile; Li, Jiufeng; Liu, Jie; Yang, Jin‐Kui; Wang, Jia; Lian, Qizhou; Xu, Aimin

doi:10.1038/s42255-022-00572-2

Cited by 27 publications

(9 citation statements)

References 76 publications

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“…Klotho may counteract the detrimental effects of hyperglycemia on cognition through diverse mechanisms ( Figure 3 ). By increasing insulin receptor affinity, klotho can enhance insulin sensitivity and restore neuronal insulin signaling ( 28 , 29 ). Through regulating redox systems, klotho suppresses ROS generation and inhibits ROS-induced activation of p38 MAPK/JNK pathways, curbing aberrant phosphorylation of tau ( 11 ).…”

Section: Discussionmentioning

confidence: 99%

Revisiting the mechanisms linking blood glucose to cognitive impairment: new evidence for the potential important role of klotho

Liu,

Li,

Chen

et al. 2024

Front. Endocrinol.

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BackgroundThe association between blood glucose and cognition is controversial. Klotho is an anti-aging protein with neural protective effects. This study aimed to use a population-based study to disentangle the relationship between blood glucose levels and cognitive function in older adults, and to explore the role of klotho in it.MethodsA total of 1445 eligible participants from National Health and Nutrition Examination Survey (NHANES) 2011-2014 were included in our study. Cognitive function was assessed by Digit Symbol Substitution Test (DSST) and categorized into four quartiles (Q1-Q4). General characteristics and laboratory test results including serum klotho concentration and blood glucose levels were collected. Associations of cognitive function and klotho levels with blood glucose concentrations were explored through multivariate linear regression models. Mediation models were constructed to figure out the mediating role of klotho.ResultsAll three multivariate linear regression models showed a negative correlation between blood glucose and cognitive function. (Model 1, β=-0.149, 95%CI: -0.202,-0.096, p=0.001; Model 2, β=-0.116, 95%CI: -0.167,-0.065, p=0.001; Model 3, β=-0.007, 95%CI: -0.118,-0.023, p=0.003). Mediation analysis showed that klotho mediated the statistical association between blood glucose level and cognitive function with proportions (%) of 12.5.ConclusionHigher blood glucose levels are associated with poorer cognitive performance in non-diabetic older adults, partially mediated through lower klotho levels.

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Section: Discussionmentioning

confidence: 99%

Revisiting the mechanisms linking blood glucose to cognitive impairment: new evidence for the potential important role of klotho

Liu,

Li,

Chen

et al. 2024

Front. Endocrinol.

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“…Afterward, 5 mL of HBSS was added, and the mixture was centrifuged at 2000 rpm for 20 min at 4 °C. The isolated islets, located between histopaque and HBSS, were collected, passed through a 70 μm cell strainer, and selected under a microscope [ 30 ]. These isolated islets were cultured in CMRL1066 (X018I0, IcellTrans, Wenzhou, China) supplemented with 10% FBS.…”

Section: Methodsmentioning

confidence: 99%

Human Menstrual Blood-Derived Stem Cells Protect against Tacrolimus-Induced Islet Dysfunction via Cystathionine β-Synthase Mediated IL-6/STAT3 Inactivation

Fu,

Zhang,

Zhang

et al. 2024

Biomolecules

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Diabetes imposes a huge burden worldwide. Islet transplantation is an alternative therapy for diabetes. However, tacrolimus, a kind of immunosuppressant after organ transplantation, is closely related to post-transplant diabetes mellitus. Mesenchymal stem cells (MSCs) have attracted interest for their potential to alleviate diabetes. In vivo experiments revealed that human menstrual blood-derived stem cells (MenSCs) treatment improved tacrolimus-induced blood glucose, body weight, and glucose tolerance disorders in mice. RNA sequencing was used to analyze the potential therapeutic targets of MenSCs. In this study, we illustrated that cystathionine β-synthase (CBS) contributed to tacrolimus -induced islet dysfunction. Using β-cell lines (MIN6, β-TC-6), we demonstrated that MenSCs ameliorated tacrolimus-induced islet dysfunction in vitro. Moreover, MenSC reduced the tacrolimus-induced elevation of CBS levels and significantly enhanced the viability, anti-apoptotic ability, glucose-stimulated insulin secretion (GSIS), and glycolytic flux of β-cells. We further revealed that MenSCs exerted their therapeutic effects by inhibiting CBS expression to activate the IL6/JAK2/STAT3 pathway. In conclusion, we showed that MenSCs may be a potential strategy to improve tacrolimus-induced islet dysfunction.

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“… 47 , 49 , 50 The observations suggest that the ablation of β-Klotho may weaken the effects of FGF21, and β-Klotho can improve insulin signaling independently by reducing lysosomal degradation and activating glycolytic pathways. 51 In addition, FGF21/β-Klotho signaling also stimulates glutamatergic neurons and leptin signals to regulate the energy homeostasis. 52 Although β-Klotho is a prerequisite for the function of FGF21, extracellular regulated protein kinase (ERK) phosphorylation may be the key point in the metabolic cascade triggered by FGF21/β-Klotho signaling.…”

Section: The Mechanism Of Action and Biological Role Of Fgf21mentioning

confidence: 99%

Fibroblast growth factor 21: An emerging pleiotropic regulator of lipid metabolism and the metabolic network

Zou

et al. 2024

Genes & Diseases

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β-Klotho promotes glycolysis and glucose-stimulated insulin secretion via GP130

Cited by 27 publications

References 76 publications

Revisiting the mechanisms linking blood glucose to cognitive impairment: new evidence for the potential important role of klotho

Revisiting the mechanisms linking blood glucose to cognitive impairment: new evidence for the potential important role of klotho

Human Menstrual Blood-Derived Stem Cells Protect against Tacrolimus-Induced Islet Dysfunction via Cystathionine β-Synthase Mediated IL-6/STAT3 Inactivation

Fibroblast growth factor 21: An emerging pleiotropic regulator of lipid metabolism and the metabolic network

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