Effect of semaglutide and empagliflozin on cognitive function and hippocampal phosphoproteomic in obese mice DOI Creative Commons

Xiaoyi Chen,

Shuchun Chen, Zelin Li

и другие.

Frontiers in Pharmacology, Год журнала: 2023, Номер 14

Опубликована: Март 17, 2023

Objective: Based on the 4D label-free phosphoproteomic technique, we examined differences in cognitive function and hippocampal phosphorylated protein expression high-fat diet-induced obese mice after intervention of semaglutide empagliflozin, as well effects both activity mice's tissues signaling pathways involved. Methods: Thirty-two C57BL/6JC male were assigned to two groups randomly: A control group (group C, 10% energy is from fat, n = 8) a diet H, 60% 24). The screened 12 weeks feeding based criterion that bodyweight fat rich was greater than or equal 20% average body weight blank group. Group H separate into (n 8), Semaglutide S, empagliflozin E, 8). For total weeks, S received 30 nmol/kg/d intraperitoneally, E 10 mg/kg/d via gavage, C amounts saline by intraperitoneal injection gavage. At end treatment, appraised for employing Morris water maze (MWM), serum fasting glucose, lipids, inflammatory parameters measured. phosphoproteomics method employed screen differential phosphoproteins loci different treatment groups, bioinformatics used analyze biological processes, pathways, related protein-protein interaction (PPI) network analysis these differentially proteins. Results: In comparison normal controls, escape latency induced prolonged, percentage swimming time target quadrant reduced, number times crossing platform whereas reduced latency, increase swim frequency passing through area, although there little difference effect drugs. results showed 20,493 unique peptides, representing 21,239 phosphorylation sites 4,290 Further revealed proteins corresponding are jointly distributed such dopaminergic synapses axon guidance, involved processes neuronal projection development, synaptic plasticity, axonogenesis. Notably, key factors voltage-dependent L-type calcium channel subunit alpha-1D (CACNA1D), P/Q-type alpha-1A (CACNA1A), N-type alpha-1B (CACNA1B) all found be synapse pathway, their upregulated empagliflozin. Conclusion: We first decreased CACNA1D, CACNA1A, CACNA1B serine phosphorylation, which may affect mice. increased

Язык: Английский

SGLT2 Inhibition via Empagliflozin Improves Endothelial Function and Reduces Mitochondrial Oxidative Stress: Insights From Frail Hypertensive and Diabetic Patients DOI Open Access
Pasquale Mone, Fahimeh Varzideh, Stanislovas S. Jankauskas

и другие.

Hypertension, Год журнала: 2022, Номер 79(8), С. 1633 - 1643

Опубликована: Июль 13, 2022

Frailty is a multidimensional condition often diagnosed in older adults with hypertension and diabetes, both these conditions are associated endothelial dysfunction oxidative stress. We investigated the functional role of SGLT2 (sodium glucose cotransporter 2) inhibitor empagliflozin frail diabetic hypertensive adults.

Язык: Английский

Процитировано

133
Type 2 diabetes mellitus-associated cognitive dysfunction: Advances in potential mechanisms and therapies DOI
Ailin Luo, Zheng Xie, Yue Wang

и другие.

Neuroscience & Biobehavioral Reviews, Год журнала: 2022, Номер 137, С. 104642 - 104642

Опубликована: Март 30, 2022

Язык: Английский

Процитировано

82
High HDL (High-Density Lipoprotein) Cholesterol Increases Cardiovascular Risk in Hypertensive Patients DOI Open Access
Valentina Trimarco, Raffaele Izzo, Carmine Morisco

и другие.

Hypertension, Год журнала: 2022, Номер 79(10), С. 2355 - 2363

Опубликована: Сен. 7, 2022

Emerging evidence suggests that elevated circulating levels of HDL-C (high-density lipoprotein cholesterol) could be linked to an increased mortality risk. However, the best our knowledge, relationship between and specific cardiovascular events has never been investigated in patients with hypertension.To fill this knowledge gap, we analyzed hypertensive within Campania Salute Network Southern Italy.We studied 11 987 hypertension, who were followed for 25 534 person-years. Our population was divided 3 groups according plasma levels: HDL-C<40 mg/dL (low HDL-C); 40 80 (medium HDL-C>80 (high HDL-C). At follow-up analysis, adjusting potential confounders, observed a total 245 significantly risk low group high arm compared medium group. The spline analysis revealed nonlinear U-shaped association outcomes. Interestingly, associated not confirmed female patients.Our data demonstrate there is male hypertension.

Язык: Английский

Процитировано

75
Association of Sodium–Glucose Cotransporter 2 Inhibitors With Time to Dementia: A Population-Based Cohort Study DOI Open Access
Che‐Yuan Wu,

Carina Iskander,

Christa Wang

и другие.

Diabetes Care, Год журнала: 2022, Номер 46(2), С. 297 - 304

Опубликована: Дек. 12, 2022

OBJECTIVE Type 2 diabetes (T2D) increases dementia risk, but clear evidence to recommend interventions that can mitigate risk remains lacking. This population-based retrospective cohort study aimed determine whether new use of sodium–glucose cotransporter (SGLT2) inhibitors compared with dipeptidyl peptidase 4 (DPP-4) was associated lower risk. RESEARCH DESIGN AND METHODS Ontario residents aged ≥66 years who were users an SGLT2 inhibitor or a DPP-4 from 1 July 2016 31 March 2021 entered the cohort. Incident identified using validated algorithm for Alzheimer’s disease and related dementias. Propensity score–weighted Cox proportional hazards models used obtain adjusted hazard ratios (aHR) CIs time incident dementia. To address reverse causality latency, observation window started at 1-year lag entry. The primary analysis followed intention-to-treat exposure definition, secondary as-treated performed. RESULTS Among 106,903 individuals, (14.2/1,000 person-years; aHR 0.80 [95% CI 0.71–0.89]) over mean follow-up 2.80 When stratified by different inhibitors, dapagliflozin exhibited lowest (aHR 0.67 0.53–0.84]), empagliflozin 0.78 0.69–0.89]), whereas canagliflozin showed no association 0.96 0.80–1.16]). observed larger 0.66 0.57–0.76]) than analysis. CONCLUSIONS in older people T2D. Randomized controlled trials are warranted.

Язык: Английский

Процитировано

71
Cognitive Impairment in Patients With Cardiac Disease: Implications for Clinical Practice DOI
Astrid C. van Nieuwkerk, Ronak Delewi,

Frank J. Wolters

и другие.

Stroke, Год журнала: 2023, Номер 54(8), С. 2181 - 2191

Опубликована: Июнь 5, 2023

Cognitive impairment is common in patients with cardiovascular disease. One 3 presenting at cardiology clinics have some degree of cognitive impairment, depending on the cardiac condition, comorbidities, and age. In up to half these cases may go unrecognized; however, it affect self-management treatment adherence. The high prevalence disease likely due shared risk factors, as well direct consequences dysfunction brain. Moreover, interventions beneficial adverse effects functioning. this review, we describe factors for several conditions: heart failure, coronary artery disease, aortic valve stenosis. We discuss potential guideline-based treatments cognition identify open questions unmet needs. Given unrecognized patients, recommend a stepwise approach improve detection management impairment.

Язык: Английский

Процитировано

48
Sodium-glucose cotransporter-2 inhibitors and their potential role in dementia onset and cognitive function in patients with diabetes mellitus: a systematic review and meta-analysis DOI Creative Commons

Y J Youn,

Seung Yeon Kim,

Hyun‐Jeong Jeong

и другие.

Frontiers in Neuroendocrinology, Год журнала: 2024, Номер 73, С. 101131 - 101131

Опубликована: Фев. 16, 2024

This systematic review and meta-analysis aimed to determine the association between use of sodium-glucose cotransporter 2 (SGLT-2) inhibitors dementia onset as well cognitive function in patients with diabetes mellitus. We comprehensively searched MEDLINE, Embase, CENTRAL databases select relevant studies published up August 2023. The SGLT-2 significantly lowers risk compared SGLT-2i non-users (Hazard ratio: 0.68, 95 % CI: 0.50-0.92). Furthermore, our findings indicated a positive effect inhibitor on score improvement, demonstrated by standardized mean difference 0.88 (95 0.32-1.44), particularly among populations mild impairment or dementia. indicate potential role reducing These underscore need for well-controlled large clinical trials future research this field.

Язык: Английский

Процитировано

20
Cognitive Impairment in Heart Failure: A Heart Failure Society of America Scientific Statement DOI Open Access
Parag Goyal, Robert J. DiDomenico, Susan J. Pressler

и другие.

Journal of Cardiac Failure, Год журнала: 2024, Номер 30(3), С. 488 - 504

Опубликована: Март 1, 2024

Язык: Английский

Процитировано

20
Treatment of chronic kidney disease in older populations DOI
Seiji Kishi, Hiroyuki Kadoya, Naoki Kashihara

и другие.

Nature Reviews Nephrology, Год журнала: 2024, Номер 20(9), С. 586 - 602

Опубликована: Июль 8, 2024

Язык: Английский

Процитировано

16
Impact of Sodium Glucose Cotransporter 2 Inhibitors (SGLT2i) Therapy on Dementia and Cognitive Decline DOI Creative Commons

Antonio Lardaro,

L. Quarta,

Stefania Pagnotta

и другие.

Biomedicines, Год журнала: 2024, Номер 12(8), С. 1750 - 1750

Опубликована: Авг. 3, 2024

Dementia is an age-related syndrome characterized by the progressive deterioration of cognition and capacity for independent living. Diabetes often associated with cognitive decline shares similar pathophysiological mechanisms dementia, such as systemic inflammation, oxidative stress, insulin resistance, advanced glycation end-products formation. Therefore, adequate diabetes management may reduce risk decline, especially in patients other comorbidities factors. The sodium glucose cotransporter inhibitors (SGLT2i) regulate renal reabsorption blocking SGLT2 cotransporters located proximal tubules, causing glycosuria intraglomerular pressure reduction. Their use helps to lower blood modifying water homeostasis; these drugs are also commonly used treatment heart failure chronic kidney disease, while recently, a potential neuroprotective role central nervous system has been suggested. aim our scoping review analyze current evidence about effects SGLT2i adult patients. We performed literature evaluate effect on mild impairment (MCI) Alzheimer's disease incidence progression. screening process was through different searches PubMed EMBASE, evaluating original works published up January 2024. In conclusion, could be diabetes, reducing or progression MCI dementia. Further prospective studies needed validate this hypothesis effectiveness class normal glycemic profile

Язык: Английский

Процитировано

15
Amyloid-β and heart failure in Alzheimer’s disease: the new vistas DOI Creative Commons
Hayder M. Al‐kuraishy, Ghassan M. Sulaiman, Hamdoon A. Mohammed

и другие.

Frontiers in Medicine, Год журнала: 2025, Номер 12

Опубликована: Фев. 4, 2025

Alzheimer’s disease (AD) is the most common cause of dementia and represents 75% all types. AD neuropathology due to progressive deposition extracellular amyloid-beta (A β ) peptide intracellular hyperphosphorylated tau protein. The accumulated Aβ forms amyloid plaques, while protein neurofibrillary tangles (NFTs). Both plaques NFTs are hallmarks neuropathology. fundamental mechanism involved in pathogenesis still elusive, although more conceivable theory. Aβ-induced neurodegeneration associated neuroinflammation, oxidative stress, endoplasmic reticulum stress (ER), mitochondrial dysfunction contribute development cognitive impairment dementia. Of note, not only originated from brain but also produced peripherally and, via blood–brain barrier (BBB), can accumulate result AD. It has been shown that cardiometabolic conditions such as obesity, type 2 diabetes (T2D), heart failure (HF) regarded possible risk factors for other types dementia, vascular HF-induced chronic cerebral hypoperfusion, inflammation induce progression Interestingly, a systemic causes which turn affects peripheral organs, including heart. through deranged BBB be transported into circulation heart, leading HF. These findings suggest close relationship between However, exact AD-induced HF fully elucidated. Therefore, this review aims discuss link regarding potential role

Язык: Английский

Процитировано

3