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

Xiaoyi Chen,

Shuchun Chen, Zelin Li

et al.

Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 14

Published: March 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

Language: Английский

Empagliflozin Improves the MicroRNA Signature of Endothelial Dysfunction in Patients with Heart Failure with Preserved Ejection Fraction and Diabetes DOI Open Access
Pasquale Mone, Angela Lombardi, Urna Kansakar

et al.

Journal of Pharmacology and Experimental Therapeutics, Journal Year: 2022, Volume and Issue: 384(1), P. 116 - 122

Published: July 25, 2022

Endothelial dysfunction represents a key mechanism underlying heart failure with preserved ejection fraction (HFpEF), diabetes mellitus (DM), and frailty. However, reliable biomarkers to monitor endothelial in these patients are lacking. In this study, we evaluated the expression of panel circulating microRNAs (miRs) involved regulation function frail older adults HFpEF DM that were treated for 3 months empagliflozin, metformin, or insulin. We identified unique pattern miRs significantly regulated compared healthy controls after treatment SGLT2 inhibitor empagliflozin. Three downregulated (miR-126, miR-342-3p, miR-638) two upregulated (miR-21 miR-92) controls. Strikingly, reduced 3-month empagliflozin whereas no significant differences profile miRNAs detected metformin Significance Statement have first time signature microRNA functionally is diabetes. The caused modification some direction was opposite what observed patients, indicating rescue function. Our findings relevant inasmuch as novel disease well response therapy been established.

Language: Английский

Citations

66
Hyperglycemia and Physical Impairment in Frail Hypertensive Older Adults DOI Creative Commons

Antonella Pansini,

Angela Lombardi,

Maria Morgante

et al.

Frontiers in Endocrinology, Journal Year: 2022, Volume and Issue: 13

Published: April 14, 2022

Frailty is a multidimensional condition typical of elders. Frail older adults have high risk functional decline, hospitalization, and mortality. Hypertension one the most common comorbidities in Hyperglycemia (HG) frequently observed frail adults, represents an independent predictor worst outcomes, with or without diabetes mellitus (DM). We aimed at investigating impact HG on physical impairment frailty.We studied consecutive frailty hypertension ASL (local health unit Italian Ministry Health) Avellino, Italy, from March 2021 to September 2021. Exclusion criteria were: age <65 years, no frailty, hypertension, left ventricular ejection fraction <25%, previous myocardial infarction, primary percutaneous coronary intervention and/or artery bypass grafting. Blood glucose, Hb1Ac, creatinine were measured all patients. Physical was assessed applying Fried Criteria; we performed 5-meter gait speed (5mGS) test patients.149 hypertensive enrolled study, which 82 had normoglycemia (NG), 67 HG. significantly slower 5mGS group compared NG (0.52 ± 0.1 vs. 0.69 0.06; p<0.001). Moreover, found strong significant correlation between glycemia (r: 0.833; A multivariable linear regression analysis using as dependent variable revealed association (p<0.001) after adjusting for likely confounders.HG drives independently DM.

Language: Английский

Citations

43
Treatment of type 2 diabetes patients with heart conditions DOI
Gülali Aktaş, Burçin Meryem Atak Tel,

Ramiz Tel

et al.

Expert Review of Endocrinology & Metabolism, Journal Year: 2023, Volume and Issue: 18(3), P. 255 - 265

Published: April 18, 2023

While type 2 diabetes mellitus (T2DM) increases the risk of cardiac complications, treatment choices may increase or decrease rates events. In present review, we comprehensively discussed options diabetic subjects with conditions.Current evidence related to in situations has been reviewed. Clinical trials and meta-analyses on safety anti-diabetic medicines are discussed. Treatment proven benefits those at least without associated increased were drawn from clinical trials; studies recent medical literature basis suggestions review.We can suggest that hypoglycemia extreme hyperglycemia should be avoided acute ischemic heart conditions. Certain options, especially sodium-glucose cotransporter-2 (SGLT2) inhibitors, reduce overall cardiovascular mortality hospitalization due failure. Therefore, physicians choose SGLT2 inhibitors as first-line option patients failure who have a high development. T2DM atrial fibrillation (AF), metformin pioglitazone seem AF population.

Language: Английский

Citations

31
miR-181c targets Parkin and SMAD7 in human cardiac fibroblasts: Validation of differential microRNA expression in patients with diabetes and heart failure with preserved ejection fraction DOI
Stanislovas S. Jankauskas, Pasquale Mone, Roberta Avvisato

et al.

Mechanisms of Ageing and Development, Journal Year: 2023, Volume and Issue: 212, P. 111818 - 111818

Published: April 27, 2023

Language: Английский

Citations

30
SGLT2 inhibitors: a novel therapy for cognitive impairment via multifaceted effects on the nervous system DOI Creative Commons
Jiaqi Mei,

Yi Li,

Liyan Niu

et al.

Translational Neurodegeneration, Journal Year: 2024, Volume and Issue: 13(1)

Published: Aug. 9, 2024

The rising prevalence of diabetes mellitus has casted a spotlight on one its significant sequelae: cognitive impairment. Sodium-glucose cotransporter-2 (SGLT2) inhibitors, originally developed for management, are increasingly studied their benefits. These benefits may include reduction oxidative stress and neuroinflammation, decrease amyloid burdens, enhancement neuronal plasticity, improved cerebral glucose utilization. multifaceted effects the relatively favorable side-effect profile SGLT2 inhibitors render them promising therapeutic candidate disorders. Nonetheless, application impairment is not without limitations, necessitating more comprehensive research to fully determine potential treatment. In this review, we discuss role in neural function, elucidate diabetes-cognition nexus, synthesize current knowledge based animal studies clinical evidence. Research gaps proposed spur further investigation.

Language: Английский

Citations

13
The effect of sodium glucose Co-transport 2 inhibitors on cognitive impairment and depression in type 2 diabetes mellitus patients DOI Creative Commons

Ashurova Nodirahon,

Haya Majid, Swati Waghdhare

et al.

Clinical Epidemiology and Global Health, Journal Year: 2024, Volume and Issue: 26, P. 101555 - 101555

Published: Feb. 19, 2024

Background and aimType 2 diabetes mellitus (T2DM) is a prevalent metabolic disorder often associated with thyroid dysfunction. Sodium-glucose co-transport (SGLT2) inhibitors, novel class of medications for T2DM, have shown potential effects on various physiological systems, including the central nervous system (CNS). This study aimed to investigate impact SGLT2 inhibitors cognition depression in T2DM patients its association dysfunction.MethodsA case-control observational was conducted involving 138 participants, cases healthy controls. Data demographics, anthropometric measures, parameters, function, (Physical Health questionnaire- 9), (Montreal Cognitive Assessment questionnaire) were collected. Subgroup analysis compared different inhibitors.ResultsT2DM taking exhibited significantly higher levels thyroid-stimulating hormone (TSH) controls (p < 0.001). Additionally, showed prevalence mild moderate 0.001, odds ratio = 1.74) cognitive impairment 0.039, 1.32) revealed varying among function.ConclusionSGLT2 may unexpected consequences depression, cognition. These findings highlight need comprehensive patient care, mental health assessment, when prescribing inhibitors. Further research warranted elucidate underlying mechanisms optimize management using these medications.

Language: Английский

Citations

10
Physical decline and cognitive impairment in frail hypertensive elders during COVID-19 DOI Open Access
Pasquale Mone,

Antonella Pansini,

Salvatore Frullone

et al.

European Journal of Internal Medicine, Journal Year: 2022, Volume and Issue: 99, P. 89 - 92

Published: March 14, 2022

Language: Английский

Citations

37
SGLT2-inhibitors are effective and safe in the elderly: The SOLD study DOI
Maria Elena Lunati, Vincenzo Cimino,

Alessandra Gandolfi

et al.

Pharmacological Research, Journal Year: 2022, Volume and Issue: 183, P. 106396 - 106396

Published: Aug. 12, 2022

Language: Английский

Citations

37
Efficacy and safety profile of SGLT2 inhibitors in the elderly: How is the benefit/risk balance? DOI
André Scheen, Fabrice Bonnet

Diabetes & Metabolism, Journal Year: 2023, Volume and Issue: 49(2), P. 101419 - 101419

Published: Jan. 11, 2023

Language: Английский

Citations

20
Extended-release metformin improves cognitive impairment in frail older women with hypertension and diabetes: preliminary results from the LEOPARDESS Study DOI Creative Commons
Pasquale Mone,

Giuseppe Martinelli,

Angela Lucariello

et al.

Cardiovascular Diabetology, Journal Year: 2023, Volume and Issue: 22(1)

Published: April 21, 2023

Abstract Background Women have a high risk of frailty independently age and menopause state. Diabetes hypertension increase the cognitive impairment. Metformin has been employed in post-menopausal women some reports shown encouraging effects terms attenuated frailty. However, impact on performance recently introduced extended-release formulation metformin never explored. Methods We studied consecutive frail hypertensive diabetic older presenting at ASL (local health authority Italian Ministry Health) Avellino, Italy, from June 2021 to August 2022, who were treated or not with metformin. included control group males diabetes regular Results A total 145 patients successfully completed study. At end 6-month follow-up, we observed significantly different compared baseline (p: 0.007). Then, follow-up groups significant differences between vs. untreated 0.041), men 0.016), 0.048). confirmed crucial role applying multivariable logistic analysis adjust for potential confounders. Conclusions evidenced, first time best our knowledge, favorable impairment hypertension.

Language: Английский

Citations

16