Nonenzymatic function of DPP4 in diabetes‐associated mitochondrial dysfunction and cognitive impairment

Sun, Cunwei; Xiao, Yanhua; Li, Jiaxiu; Ge, Bo; Chen, Xu; Liu, Hongbo; Zheng, Tianyuan

doi:10.1002/alz.12437

Cited by 22 publications

(11 citation statements)

References 50 publications

(94 reference statements)

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“…Hyperglycemia possibly leads to hippocampal tissue damage. An animal study ( 144 ) suggested that overexpression of Dipeptidyl peptidase-4 (DPP4) in diabetic rats may reduce peroxisome proliferator-activated receptors γ-Coactivator 1α expression, leading to mitochondrial dysfunction. Hyperglycemia may also increase the levels of inflammatory cytokines, such as interferon-γ (IFN-γ) and interleukin-6 in the hippocampus, resulting in the apoptosis of hippocampal neurons ( 145 ).…”

Section: Discussionmentioning

confidence: 99%

Brain Imaging Changes and Related Risk Factors of Cognitive Impairment in Patients With Heart Failure

Jiang

Wang

et al. 2022

Front. Cardiovasc. Med.

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Background/AimsTo explore the imaging changes and related risk factors of heart failure (HF) patients with cognitive impairment (CI).MethodsA literature search was systematically carried out in PubMed, Web of Science, Embase, and Cochrane Library. In this systematic review, important relevant information was extracted according to the inclusion and exclusion criteria. The methodological quality was assessed by three scales according to the different study types.ResultsFinally, 66 studies were included, involving 33,579 patients. In the imaging changes, the severity of medial temporal lobe atrophy (MTA) and the decrease of gray Matter (GM) volume were closely related to the cognitive decline. The reduction of cerebral blood flow (CBF) may be correlated with CI. However, the change of white matter (WM) volume was possibly independent of CI in HF patients. Specific risk factors were analyzed, and the data indicated that the increased levels of B-type natriuretic peptide (BNP)/N-terminal pro-B-type natriuretic peptide (NT-proBNP), and the comorbidities of HF, including atrial fibrillation (AF), diabetes mellitus (DM) and anemia were definitely correlated with CI in patients with HF, respectively. Certain studies had also obtained independent correlation results. Body mass index (BMI), depression and sleep disorder exhibited a tendency to be associated with CI. Low ejection fraction (EF) value (<30%) was inclined to be associated with the decline in cognitive function. However, no significant differences were noted between heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF) in cognitive scores.ConclusionBNP/NT-proBNP and the comorbidities of HF including AF, DM and anemia were inextricably correlated with CI in patients with HF, respectively. These parameters were independent factors. The severity of MTA, GM volume, BMI index, depression, sleep disorder, and low EF value (<30%) have a disposition to associated with CI. The reduction in the CBF volume may be related to CI, whereas the WM volume may not be associated with CI in HF patients. The present systematic review provides an important basis for the prevention and treatment of CI following HF.

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Section: Discussionmentioning

confidence: 99%

Brain Imaging Changes and Related Risk Factors of Cognitive Impairment in Patients With Heart Failure

Jiang

Wang

et al. 2022

Front. Cardiovasc. Med.

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“…The study showed that the expression of SIRT1 and PGC-1α in the brain of T2DM mice decreased significantly [120]. Decreased PGC-1α expression and activation in hippocampal neurons of T2DM mice leads to blocked mitochondrial biogenesis and mitochondrial dysfunction, triggers neuronal loss, and promotes cognitive impairment in diabetes [133,134]. Downregulation of PGC-1α in the hippocampus of T2DM may result from dipeptidyl peptidase-4 binding to protease-activated receptor 2 and triggering glycogen synthase kinase-3β (GSK3β) activation [133].…”

Section: Mitochondrial Biogenesismentioning

confidence: 96%

“…Decreased PGC-1α expression and activation in hippocampal neurons of T2DM mice leads to blocked mitochondrial biogenesis and mitochondrial dysfunction, triggers neuronal loss, and promotes cognitive impairment in diabetes [133,134]. Downregulation of PGC-1α in the hippocampus of T2DM may result from dipeptidyl peptidase-4 binding to protease-activated receptor 2 and triggering glycogen synthase kinase-3β (GSK3β) activation [133]. Insulin signaling has also been found to be involved in regulating PGC-1α expression, affecting mitochondrial biogenesis [135,136].…”

Section: Mitochondrial Biogenesismentioning

confidence: 99%

The Role of Mitochondrial Quality Control in Cognitive Dysfunction in Diabetes

et al. 2022

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Type 2 diabetes (T2DM) is a well known risk factor for Alzheimer’s disease. Mitochondria are the center of intracellular energy metabolism and the main source of reactive oxygen species. Mitochondrial dysfunction has been identified as a key factor in diabetes-associated brain alterations contributing to neurodegenerative events. Defective insulin signaling may act in concert with neurodegenerative mechanisms leading to abnormalities in mitochondrial structure and function. Mitochondrial dysfunction triggers neuronal energy exhaustion and oxidative stress, leading to brain neuronal damage and cognitive impairment. The normality of mitochondrial function is basically maintained by mitochondrial quality control mechanisms. In T2DM, defects in the mitochondrial quality control pathway in the brain have been found to lead to mitochondrial dysfunction and cognitive impairment. Here, we discuss the association of mitochondrial dysfunction with T2DM and cognitive impairment. We also review the molecular mechanisms of mitochondrial quality control and impacts of mitochondrial quality control on the progression of cognitive impairment in T2DM.

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“…It has been indicated that cerebral glucose hypometabolism is associated with an increased risk of DACD (Sun et al, 2021). In this study, 18 F‐FDG microPET was used to detect glucose uptake in the brain in vivo.…”

Section: Resultsmentioning

confidence: 99%

A novel natural PPARγ agonist, Gypenoside LXXV, ameliorates cognitive deficits by enhancing brain glucose uptake via the activation of Akt/GLUT4 signaling in db/db mice

Meng

Zhang

et al. 2022

Phytotherapy Research

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Targeting the PPARγ might be a potential therapeutic strategy for diabetesassociated cognitive decline (DACD). In this study, Gypenoside LXXV (GP-75), a dammarane-type triterpene compound isolated from Gynostemma pentaphyllum, was found to be a novel PPARγ agonist using a dual-luciferase reporter assay system. However, whether GP-75 has protective effects against DACD remains unknown.Interestingly, intragastric administration of GP-75 (40 mg/kg/day) for 12 weeks significantly attenuated the cognitive deficit in db/db mice. GP-75 treatment significantly improved the glucose tolerance and lipid metabolism, and suppressed neuroinflammation. Notably, GP-75 treatment dramatically increased the uptake of glucose by the brain, as detected by 18 F-FDG PET. Incubation of primary cortical neurons with GP-75 significantly increased 2-deoxyglucose uptake. In addition, GP-75 treatment markedly increased the p-Akt (Ser 473)/total Akt levels and the expression levels of PPARγ and GLUT4, while decreasing the levels of p-IRS-1 (Ser 616

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Nonenzymatic function of DPP4 in diabetes‐associated mitochondrial dysfunction and cognitive impairment

Cited by 22 publications

References 50 publications

Brain Imaging Changes and Related Risk Factors of Cognitive Impairment in Patients With Heart Failure

Brain Imaging Changes and Related Risk Factors of Cognitive Impairment in Patients With Heart Failure

The Role of Mitochondrial Quality Control in Cognitive Dysfunction in Diabetes

A novel natural PPARγ agonist, Gypenoside LXXV, ameliorates cognitive deficits by enhancing brain glucose uptake via the activation of Akt/GLUT4 signaling in db/db mice

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