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teneligliptin mitigates diabetic cardiomyopathy by inhibiting activation of the NLRP3 inflammasome

World Journal of Diabetes 2024年第4期15卷 724-734页

作者： Gu-Lao Zhang Yuan Liu Yan-Feng Liu Xian-Tao Huang Yu Tao Zhen-Huan Chen Heng-Li Lai Department of Cardiology Jiangxi Provincial People's HospitalThe First Affiliated Hospital of Nanchang Medical CollegeNanchang 330000Jiangxi ProvinceChina

BACKGROUND Diabetic cardiomyopathy(DCM),which is a complication of diabetes,poses a great threat to public health.Recent studies have confirmed the role of NLRP3(NOD-like receptor protein 3)activation in DCM development through the inflammatory response.teneligliptin is an oral hypoglycemic dipeptidyl peptidase-IV inhibitor used to treat diabetes.teneligliptin has recently been reported to have anti-inflammatory and protective effects on myocardial cells.AIM To examine the therapeutic effects of teneligliptin on DCM in diabetic mice.METHODS Streptozotocin was administered to induce diabetes in mice,followed by treatment with 30 mg/kg teneligliptin.RESULTS Marked increases in cardiomyocyte area and cardiac hypertrophy indicator heart weight/tibia length reductions in fractional shortening,ejection fraction,and heart rate;increases in creatine kinase-MB(CK-MB),aspartate transaminase(AST),and lactate dehydrogenase(LDH)levels;and upregulated NADPH oxidase 4 were observed in diabetic mice,all of which were significantly reversed by teneligliptin.Moreover,NLRP3 inflammasome activation and increased release of interleukin-1βin diabetic mice were inhibited by teneligliptin.Primary mouse cardiomyocytes were treated with high glucose(30 mmol/L)with or without teneligliptin(2.5 or 5μM)for 24 h.NLRP3 inflammasome activation.Increases in CKMB,AST,and LDH levels in glucose-stimulated cardiomyocytes were markedly inhibited by teneligliptin,and AMP(p-adenosine 5‘-monophosphate)-p-AMPK(activated protein kinase)levels were increased.Furthermore,the beneficial effects of teneligliptin on hyperglycaemia-induced cardiomyocytes were abolished by the AMPK signaling inhibitor compound C.CONCLUSION Overall,teneligliptin mitigated DCM by mitigating activation of the NLRP3 inflammasome.

关键词： Diabetic cardiomyopathy teneligliptin NLRP3 AMPK Interleukin-1β

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teneligliptin: Heralding Change in Type 2 Diabetes

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Journal of Diabetes Mellitus 2016年第2期6卷 113-131页

作者： Manish Maladkar Srividya Sankar Kushal Kamat Aristo Pharmaceuticals Pvt. Ltd. Mumbai India

“Sweet is Sweet but until it is not too Sweet”. As the sweet spoon of diabetes challenges the global population, diabetic organizations across the globe call for unanimous resonance of Diabetes Voice to tackle diabetes with healthy living. With the discovery of new pathophysiology associated with diabetes, patients are gaining access to the newer therapeutic classes. teneligliptin, a third generation DPP-4 inhibitor exhibits unique “J-shaped” structure with “anchor-lock domain” mechanism which provides potent & long duration of action. It acts like an insulin/glucagon modulator controlling blood glucose over 24 hours. It is effective in tackling short-term glycemic fluctuations and improvement in β-cell parameters is observed soon after treatment. Half-life of 26.9 hours ensures once a day administration. Because the metabolites of this drug are eliminated via renal and hepatic excretion, no dose adjustment is necessary in patients with renal impairment. Improvement in lipid profile, LV function, adiponectin levels & natriuretic effect is among the added pleiotropic benefits. With the effective glycemic control & capability for improvement in β-cell function, teneligliptin promises to be a preferable antidiabetic agent with long-term efficacy & safety in patients with type 2 diabetes. The objective of this paper is to provide a comprehensive datum analysis of teneligliptin in the management of type 2 diabetes. It summarizes the unique pharmacodynamic & pharmacokinetic advantages of teneligliptin and additionally its pleiotropic benefits of cardioprotection. It provides a comprehensive comparison of teneligliptin vis-à-vis other gliptins in the class & provides a concise summary of all clinical trials till the date with teneligliptin monotherapy & combination with other antidiabetic drugs.

关键词： teneligliptin DPP-4 Inhibitors GLP-1 β-Cell Preservation Pleiotropic Benefits Gliptins

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Dipeptidyl peptidase-4: A key player in chronic liver disease

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World Journal of Gastroenterology 2013年第15期19卷 2298-2306页

作者： Minoru Itou Takumi Kawaguchi Eitaro Taniguchi Michio Sata Division of Gastroenterology Department of MedicineKurume University School of MedicineKurume 830-0011Japan Division of Gastroenterology Department of Medicine and Department of Digestive Disease Information and ResearchKurume University School of MedicineKurume 830-0011Japan

Dipeptidyl peptidase-4 (DPP-4) is a membrane-associated peptidase, also known as CD26. DPP-4 has widespread organ distribution throughout the body and exerts pleiotropic effects via its peptidase activity. A representative target peptide is glucagon-like peptide-1, and inactivation of glucagon-like peptide-1 results in the development of glucose intolerance/diabetes mellitus and hepatic steatosis. In addition to its peptidase activity, DPP-4 is known to be associated with immune stimulation, binding to and degradation of extracellular matrix, resistance to anti-cancer agents, and lipid accumulation. The liver expresses DPP-4 to a high degree, and recent accumulating data suggest that DPP-4 is involved in the development of various chronic liver diseases such as hepatitis C virus infection, non-alcoholic fatty liver disease, and hepatocellular carcinoma. Furthermore, DPP-4 occurs in hepatic stem cells and plays a crucial role in hepatic regeneration. In this review, we described the tissue distribution and various biological effects of DPP-4. Then, we discussed the impact of DPP-4 in chronic liver disease and the possible therapeutic effects of a DPP-4 inhibitor.

关键词： Incretin Viral hepatitis Insulin resistance Steatohepatitis Cancer Sitagliptin Vildagliptin Alogliptin teneligliptin Linagliptin

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Drug interactions of dipeptidyl peptidase 4 inhibitors involving CYP enzymes and P-gp efflux pump

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World Journal of Meta-Analysis 2019年第4期7卷 156-161页

作者： Naina Mohamed Pakkir Maideen Department of Pharmacy Dubai Health Authority

Dipeptidyl peptidase 4(DPP4) inhibitors are oral antidiabetic drugs approved to manage type 2 diabetes mellitus. Saxagliptin is a substrate of CYP3A4/5 enzymes while other DPP4 inhibitors such as sitagliptin, linagliptin, gemigliptin and teneligliptin are weak substrates of CYP3A4. DPP4 inhibitors have also been identified as substrates of P-gp. Hence, the drugs inhibiting or inducing CYP3A4/5 enzymes and/or P-gp can alter the pharmacokinetics of DPP4 inhibitors. This review is aimed to identify the drugs interacting with DPP4 inhibitors. The plasma concentrations of saxagliptin have been reported to be increased significantly by the concomitant administration of ketoconazole or diltiazem while no significant interactions between various DPP4 inhibitors and drugs like warfarin, digoxin or cyclosporine have been identified.

关键词： Drug interactions Sitagliptin Saxagliptin Linagliptin Gemigliptin teneligliptin Vildagliptin Anagliptin CYP3A4 P-gp efflux pump

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降糖药特力利汀(teneligliptin)

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世界临床药物 2013年第10期 641-641页

1商品名Tenelia2开发与上市厂商田边三菱制药公司研制,2012年9月在日本首次上市。3适应证本品为二肽基肽酶-Ⅳ(DPP-4)抑制剂,用于2型糖尿病的治疗。4药理4.1作用机制本品通过抑制DPP-4的活性阻碍胰高血糖素样肽-1(GLP-1)的降解,以提高... 详细信息

1商品名Tenelia2开发与上市厂商田边三菱制药公司研制,2012年9月在日本首次上市。3适应证本品为二肽基肽酶-Ⅳ(DPP-4)抑制剂,用于2型糖尿病的治疗。4药理4.1作用机制本品通过抑制DPP-4的活性阻碍胰高血糖素样肽-1(GLP-1)的降解,以提高血液中GLP-1的浓度发挥降糖作用。4.2药动学健康成人,早餐前30 min一日1次口服本品20 mg,连续7 d,血药浓度达到稳定水平;饭后服用本品20 mg,

关键词：本品型糖尿病健康成人格列美脲吡格列酮降糖药降血糖药 teneligliptin 低血糖症状血糖水平

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