The sodium-glucose cotransporter 2 inhibitor tofogliflozin induces vasodilation by activating Kv channels, the SERCA pump, and the sGC/cGMP pathway DOI Creative Commons
Won Sun Park,

Wenwen Zhuang,

Minju Park

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Дек. 13, 2024

OBJECTIVE: Tofogliflozin is a sodium-glucose cotransporter 2 (SGLT2) inhibitor widely used to treat T2DM, but it also exhibits cardio-protective effects. This study investigated the vasodilatory action of tofogliflozin using rabbit femoral artery rings pre-contracted with phenylephrine. APPROACH AND RESULTS: The quickly separated from and fix organ bath chamber. Subsequently, administer an that modulates vascular tension in or remove endothelium assess its impact on vasodilation. results showed concentration-dependent induction vasodilation by tofogliflozin, response remained unchanged following endothelial removal, pretreatment nitric oxide synthase (NOS) L-NAME, inhibition low- intermediate-conductance Ca2+-activated K+ channels (SKCa IKCa) apamin combination TRAM-34. Furthermore, voltage-dependent (Kv) channel 4-AP reduced effects whereas ATP-sensitive (KATP) glibenclamide large-conductance (BKCa) paxilline did not. Notably, our findings indicated Kv7.X, rather than Kv1.5 Kv2.1, primary Kv subtype involved tofogliflozin-induced were significantly inhibited arterial pretreated sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) pump inhibitors thapsigargin cyclopiazonic acid (CPA). Tofogliflozin-induced was unaltered exposed adenylyl cyclase SQ 22536, protein kinase A (PKA) KT 5720, G (PKG) 582 effectively soluble guanylyl (sGC) ODQ. CONCLUSIONS: These suggest mediated activation SERCA pump, sGC/cGMP pathway, channels, not PKA signaling other endothelium-dependent mechanisms.

Язык: Английский

Modulatory role of exogenous arachidonic acid in periodontitis with type 2 diabetes mellitus mice DOI Creative Commons
Xiaomin Chen,

Yeqing He,

Yuxi Zhou

и другие.

BMC Oral Health, Год журнала: 2025, Номер 25(1)

Опубликована: Фев. 19, 2025

Type 2 diabetes mellitus (T2DM) exhibits a bidirectional relationship with periodontitis, wherein each condition influences the progression of other. Arachidonic acid (AA) exerts an anti-diabetic effect, while showing protective effect by regulating inflammatory response independently its metabolites. However, impact on periodontitis T2DM remains poorly understood. The mouse model was established combining high-sugar and high-fat diet streptozotocin injection, followed silk ligation to induce periodontitis. Alterations in diabetes-associated symptoms were evaluated. Micro-computed tomography used measure bone-related parameters, including distance from cementoenamel junction alveolar bone crest, volume/total volume mineral density. Targeted metabolomics analysis conducted evaluate exogenous AA serum metabolite levels mice type diabetic 16S rRNA gene sequencing utilized analyze microbial diversity. activity osteoclasts, factors expression related osteoclasts investigated using TRAP staining real-time quantitative PCR. successfully established. Following two weeks treatment, reduction fasting blood glucose observed mice. Exogenous alleviated loss it had no substantial contents AA-targeted reduced Staphylococcus subgingival flora mice, but significant community structure or Furthermore, decreased number increased IL-10 mRNA gingival tissue. may alleviate reducing increasing periodontal tissues, rather than change metabolites composition diversity microorganisms plaque. These findings provide potential therapeutic approach for prevention treatment T2DM.

Язык: Английский

Процитировано

0

Insights into the Roles of GLP-1, DPP-4, and SGLT2 at the Crossroads of Cardiovascular, Renal, and Metabolic Pathophysiology DOI Creative Commons
Melania Gaggini, Laura Sabatino,

Adrian Florentin Suman

и другие.

Cells, Год журнала: 2025, Номер 14(5), С. 387 - 387

Опубликована: Март 6, 2025

In recent years, new drugs for the treatment of type 2 diabetes (T2D) have been proposed, including glucagon-like peptide 1 (GLP-1) agonists or sodium–glucose cotransporter (SGLT2) inhibitors and dipeptidyl peptidase-4 (DPP-4) inhibitors. Over time, some these agents (in particular, GLP-1 SGLT2 inhibitors), which were initially developed their glucose-lowering actions, demonstrated significant beneficial pleiotropic effects, thus expanding potential therapeutic applications. This review aims to discuss mechanisms, GLP-1, DPP-4, SGLT2, with a particular focus on cardiorenal benefits beyond glycemic control.

Язык: Английский

Процитировано

0

The sodium-glucose cotransporter 2 inhibitor tofogliflozin induces vasodilation of rabbit femoral artery by activating Kv channels, the SERCA pump, and the sGC/cGMP pathway DOI

Wenwen Zhuang,

Minju Park,

Junsu Jeong

и другие.

European Journal of Pharmacology, Год журнала: 2025, Номер unknown, С. 177595 - 177595

Опубликована: Апрель 1, 2025

Язык: Английский

Процитировано

0

Evaluating the Impact of Tirzepatide on Clinical Outcomes in Patients With Heart Failure DOI Open Access
Mohammad Hamza Bin Abdul Malik,

Nazir Khan,

Mehreen Jawed Chowdhari

и другие.

Cureus, Год журнала: 2025, Номер unknown

Опубликована: Апрель 11, 2025

Язык: Английский

Процитировано

0

Strategy of non-drug management of metabolic syndrome, which is accompanied by prediabetes and hypertension DOI Creative Commons

Galyna Myhalchyshyn,

Iuliia Komisarenko,

A.E. Kosinov

и другие.

INTERNATIONAL JOURNAL OF ENDOCRINOLOGY (Ukraine), Год журнала: 2025, Номер 21(2), С. 179 - 184

Опубликована: Апрель 1, 2025

Background. The condition of prediabetes implies the possibility to achieve stable normal glycemic indicators in order prevent further development diabetes without using drug therapy. effectiveness and safety herbal cardioprotectors metabolic syndrome accompanied by is being comprehensively studied all over world. purpose was determine study possibilities influence natural cardioprotector, on carbohydrate lipid metabolism, as well blood pressure patients with syndrome. Materials methods. Patients were divided into 3 groups: first one (control group), diet therapy physical activity prescribed, second third — therapy, cardioprotector different dosages. Fasting glucose glycated hemoglobin (HbA1C), lipidogram monitored, quality life index assessed before treatment, after 4 8 weeks. estimated sum points self-reported EQ-5D-5L questionnaire. Results. Conducted clinical observations three selected groups showed ability harmonize a tendency reach norm reduce fasting HbA1C. In group 2, which took 2 capsules medicine twice daily, there more pronounced shift towards normalization low- high-density lipoproteins, total cholesterol triglycerides. Also, this compared 1 control group, significant hypoglycemic effect recorded: decrease from 6.22 ± 0.13 5.22 0.08 mmol/l (р < 0.05), allows us reasonably assume existence certain dose-dependent cardioprotector. Conclusions. Herbal has shown non-medicinal correction manifestations and, all, prediabetes. Due high profile active ingredients remedy, practitioners can fully use potential non-pharmacological

Язык: Английский

Процитировано

0

Risk factors for urinary tract infection in elderly patients with type 2 diabetes: A protocol for systematic review and meta-analysis DOI Creative Commons

Hairong Jia,

Wenhao Su,

Jiaqi Zhang

и другие.

PLoS ONE, Год журнала: 2024, Номер 19(9), С. e0310903 - e0310903

Опубликована: Сен. 26, 2024

Introduction Type 2 diabetes mellitus (T2DM) is a frequent chronic condition among the elderly, which increasing their susceptibility to infection. Urinary tract infection (UTI) one of most prevalent infections older people with T2DM. However, association between geriatric T2DM and risk UTI has not been thoroughly researched still contentious. Consequently, this protocol describes systematic review pinpoint primary factors for elderly Our goal improve recommendations creation targeted treatment interventions by examining in individuals Methods analysis We will search 4 English literature databases (PubMed, Embase, Web Science, Cochrane Library) 3 major Chinese (CNKI, WanFang, VIP) from establishment database June 20, 2024. Systematic evaluation meta-analysis be conducted on cohort case-control studies exploring occurrence determinants diagnosed The main focus identifying diabetic patients. Two researchers independently articles, collect data, evaluate quality potential bias study inclusion. use RevMan V.5.4 software analyze data. included assessed using Newcastle-Ottawa scale. In addition, GRADE (Grade Recommendations, Assessment, Development, Evaluation) method used examine evidence each exposure outcome interest. Discussion This aims illuminate various associated patients By thorough investigation, we hope provide more comprehensive reference medical professionals researchers, thereby supporting implementation effective preventive strategies against improving overall nursing outcomes specific patient population. Trail registration PROSPERO ( CRD42024559129 ).

Язык: Английский

Процитировано

2

Translational Science in Vascular Aging: From Bench to Bedside—Insights from a VascAgeNet Roundtable DOI Creative Commons
Elisabetta Bianchini, Lynn Roth, Pierre Boutouyrie

и другие.

Artery Research, Год журнала: 2024, Номер 30(1)

Опубликована: Сен. 30, 2024

Abstract Translating vascular aging research from bench to bedside presents both significant opportunities and challenges. This paper summarizes insights a roundtable discussion at the Artery 23 conference, featuring perspectives basic science, clinical trials, regulation, industry. The main conclusions of are as follows: science must align with relevance, using appropriate animal models standardized measurement techniques. Pragmatic registry-based trials offer viable alternatives traditional randomized controlled facilitating real-world applicability. regulatory landscape, particularly for software medical devices, evolve keep pace technological advancements like artificial intelligence. Industry efforts focus on developing devices or solutions assessment treatment strategies, yet face hurdles in large-scale adoption reimbursement. Despite progress, development pharmacological interventions mitigate remains critical need. underscores importance interdisciplinary collaboration overcome barriers translate scientific discoveries into practice effectively.

Язык: Английский

Процитировано

1

Development of an HPLC Method through the QbD Approach for the Quantification of Honokiol and Metformin Hydrochloride – Method Validation and Pharmaceutical Applications on Oral Dosage Forms DOI Open Access
Mousa Sha’at, A Spac, Iulian Stoleriu

и другие.

Опубликована: Июль 9, 2024

For quantitative determination of honokiol (HNK) and metformin hydrochloride (M-HCl) by HPLC from formulations dissolution studies, a QbD approach using three factors - levels design was implemented to optimize the chromatographic conditions. To study impact each variable on peak area both compounds retention time last compound eluted, 3D response surface plots were developed. HNK M-HCl separated Thermoscientific ODS Hypersyl TM (250 x 4.6 mm, 5 μm) column mantained at 30 C, 0.02 M acetate buffer (pH = 3) / methanol (15 85, v v) as mobile phase with flow rate 1 mL/min. The injected volume 20 L, detection wavelengths 256 nm for 236 M-HCl. validation proposed method showed linearity range 4 – 1200 μg/mL (r2 0.9992) 300 0.9998), good precision (RSD &amp;lt; 2% M-HCl, in intra- inter-day studies) accuracy (mean recovery 100.09% 99.80 100.43% mean 100.12% 99.70 100.38% HNK). environmentally friendly nature confirmed evaluation method’s greenness. applied oral dosage forms studies.

Язык: Английский

Процитировано

0

The sodium-glucose cotransporter 2 inhibitor tofogliflozin induces vasodilation by activating Kv channels, the SERCA pump, and the sGC/cGMP pathway DOI Creative Commons
Won Sun Park,

Wenwen Zhuang,

Minju Park

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Дек. 13, 2024

OBJECTIVE: Tofogliflozin is a sodium-glucose cotransporter 2 (SGLT2) inhibitor widely used to treat T2DM, but it also exhibits cardio-protective effects. This study investigated the vasodilatory action of tofogliflozin using rabbit femoral artery rings pre-contracted with phenylephrine. APPROACH AND RESULTS: The quickly separated from and fix organ bath chamber. Subsequently, administer an that modulates vascular tension in or remove endothelium assess its impact on vasodilation. results showed concentration-dependent induction vasodilation by tofogliflozin, response remained unchanged following endothelial removal, pretreatment nitric oxide synthase (NOS) L-NAME, inhibition low- intermediate-conductance Ca2+-activated K+ channels (SKCa IKCa) apamin combination TRAM-34. Furthermore, voltage-dependent (Kv) channel 4-AP reduced effects whereas ATP-sensitive (KATP) glibenclamide large-conductance (BKCa) paxilline did not. Notably, our findings indicated Kv7.X, rather than Kv1.5 Kv2.1, primary Kv subtype involved tofogliflozin-induced were significantly inhibited arterial pretreated sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) pump inhibitors thapsigargin cyclopiazonic acid (CPA). Tofogliflozin-induced was unaltered exposed adenylyl cyclase SQ 22536, protein kinase A (PKA) KT 5720, G (PKG) 582 effectively soluble guanylyl (sGC) ODQ. CONCLUSIONS: These suggest mediated activation SERCA pump, sGC/cGMP pathway, channels, not PKA signaling other endothelium-dependent mechanisms.

Язык: Английский

Процитировано

0