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Sodium-glucose cotransporter-2 inhibitors and dipeptidyl peptidase-4 inhibitors on diabetic macular edema and the need for intravitreal injection 认领 引用
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作者 Yoo-Ri Chung Chungwoon Kim +1 位作者 Eunzee Lee Kihwang Lee 《International Journal of Ophthalmology(English edition)》 SCIE CAS 2025年第7期1326-1332,共7页
AIM:To investigate the effects of dipeptidyl peptidase-4 inhibitors(DPP4i)and sodium-glucose cotransporter-2 inhibitors(SGLT2i)on diabetic macular edema(DME)and the need for intravitreal injections(IVT)in patients wit... AIM:To investigate the effects of dipeptidyl peptidase-4 inhibitors(DPP4i)and sodium-glucose cotransporter-2 inhibitors(SGLT2i)on diabetic macular edema(DME)and the need for intravitreal injections(IVT)in patients with type 2 diabetes.METHODS:Data were retrospectively collected from the medical records of patients with diabetic retinopathy(DR)taking either DPP4i or SGLT2i as secondary oral hypoglycemic agents in addition to metformin between January 2019 and July 2022.We compared the prevalence of DME and the need for IVT among patients treated with DPP4i or SGLT2i.Propensity score matching was performed using the following variables:age,duration of diabetes,blood glucose control(HbA1c)level,and severity of DR.RESULTS:A total of 268 patients with DR were included in this study.More DPP4i users needed IVT than SGLT2i users(35.3%vs 18.0%,P=0.011),while the prevalence of DME was not different.The use of SGLT2i was associated with a lower need for IVT than DPP4i[odds ratio(OR)0.404,95%confidence interval(CI)0.198-0.823],and similar trends were observed after propensity score matching(OR 0.419,95%CI 0.181-0.970).However,this tendency was not significant in multiple logistic regressions.For DME,the use of DPP4i was not a significant risk factor compared to SGLT2i.CONCLUSION:The use of SGLT2i may be associated with a lower need for IVT for overall DR complications,while other factors may contribute to this effect.The effect of SGLT2i on the prevention of DME is not evident. 展开更多
关键词 diabetic macular edema diabetic retinopathy dipeptidyl peptidase-4 inhibitor intravitreal injection sodium-glucose cotransporter-2 inhibitor
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Dipeptidyl peptidase-4 inhibitor for steroid-induced diabetes 认领 引用 被引量：4
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作者 Hidekatsu Yanai Yoshinori Masui +2 位作者 Reo Yoshikawa Junwa Kunimatsu Hiroshi Kaneko 《World Journal of Diabetes》 2010年第3期99-100,共2页
The addition of the dipeptidyl peptidase-4 (DDP-4) inhibitor has been reported to achieve greater improvements in glucose metabolism with fewer adverse events compared to increasing the metformin dose in type 2 diabet... The addition of the dipeptidyl peptidase-4 (DDP-4) inhibitor has been reported to achieve greater improvements in glucose metabolism with fewer adverse events compared to increasing the metformin dose in type 2 diabetic patients. We present a patient with steroid-induced diabetes whose blood glucose levels were ameliorated by the use of the DPP-4 inhibitor, showing that the DPP-4 inhibitors may be an effective and safe oral anti-diabetic drug for steroid-induced diabetes. 展开更多
关键词 Dipeptidyl peptidase-4 Nateglinide Sitagliptin Steroid-induced diabetes
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Cardiovascular efficacy and safety of dipeptidyl peptidase-4 inhibitors:A meta-analysis of cardiovascular outcome trials 认领 引用 被引量：4
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作者 Dimitrios Ioannis Patoulias Aristi Boulmpou +5 位作者 Eleftherios Teperikidis Alexandra Katsimardou Fotios Siskos Michael Doumas Christodoulos E Papadopoulos Vassilios Vassilikos 《World Journal of Cardiology》 2021年第10期585-592,共8页
BACKGROUND Dipeptidyl peptidase-4(DPP-4)inhibitors are a generally safe and well tolerated antidiabetic drug class with proven efficacy in type 2 diabetes mellitus(T2DM).Recently,a series of large,randomized controlle... BACKGROUND Dipeptidyl peptidase-4(DPP-4)inhibitors are a generally safe and well tolerated antidiabetic drug class with proven efficacy in type 2 diabetes mellitus(T2DM).Recently,a series of large,randomized controlled trials(RCTs)addressing cardiovascular outcomes with DPP-4 inhibitors have been published.AIM To pool data from the aforementioned trials concerning the impact of DPP-4 inhibitors on surrogate cardiovascular efficacy outcomes and on major cardiac arrhythmias.METHODS We searched PubMed and grey literature sources for all published RCTs assessing cardiovascular outcomes with DPP-4 inhibitors compared to placebo until October 2020.We extracted data concerning the following“hard”efficacy outcomes:fatal and non-fatal myocardial infarction,fatal and non-fatal stroke,hospitalization for heart failure,hospitalization for unstable angina,hospitalization for coronary revascularization and cardiovascular death.We also extracted data regarding the risk for major cardiac arrhythmias,such as atrial fibrillation,atrial flutter,ventricular fibrillation and ventricular tachycardia.RESULTS We pooled data from 6 trials in a total of 52520 patients with T2DM assigned either to DPP-4 inhibitor or placebo.DPP-4 inhibitors compared to placebo led to a non-significant increase in the risk for fatal and non-fatal myocardial infarction[risk ratio(RR)=1.02,95%CI:0.94-1.11,I2=0%],hospitalization for heart failure(RR=1.09,95%CI:0.92-1.29,I2=65%)and cardiovascular death(RR=1.02,95%CI:0.93-1.11,I2=0%).DPP-4 inhibitors resulted in a non-significant decrease in the risk for fatal and non-fatal stroke(RR=0.96,95%CI:0.85-1.08,I2=0%)and coronary revascularization(RR=0.99,95%CI:0.90-1.09,I2=0%),Finally,DPP-4 inhibitors demonstrated a neutral effect on the risk for hospitalization due to unstable angina(RR=1.00,95%CI:0.85-1.18,I2=0%).As far as cardiac arrhythmias are concerned,DPP-4 inhibitors did not significantly affect the risk for atrial fibrillation(RR=0.95,95%CI:0.78-1.17,I2=0%),while they were associated with a significant increase in the risk for atrial flutter,equal to 52%(RR=1.52,95%CI:1.03-2.24,I2=0%).DPP-4 inhibitors did not have a significant impact on the risk for any of the rest assessed cardiac arrhythmias.CONCLUSION DPP-4 inhibitors do not seem to confer any significant cardiovascular benefit for patients with T2DM,while they do not seem to be associated with a significant risk for any major cardiac arrhythmias,except for atrial flutter.Therefore,this drug class should not be the treatment of choice for patients with established cardiovascular disease or multiple risk factors,except for those cases when newer antidiabetics(glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors)are not tolerated,contraindicated or not affordable for the patient. 展开更多
关键词 Dipeptidyl peptidase-4 inhibitors Cardiovascular outcomes Atrial fibrillation Atrial flutter Type 2 diabetes mellitus
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Dipeptidyl peptidase-4 inhibitor-induced autoimmune diseases:Current evidence 认领 引用 被引量：2
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作者 Ayan Roy Jayaprakash Sahoo +3 位作者 Niya Narayanan Chandhana Merugu Sadishkumar Kamalanathan Dukhabandhu Naik 《World Journal of Diabetes》 SCIE 2021年第9期1426-1441,共16页
Dipeptidyl peptidase-4 inhibitors(DPP-4i)have an important place in the management of type 2 diabetes.The DPP-4 enzyme is ubiquitously distributed throughout the human body and has multiple substrates through which it... Dipeptidyl peptidase-4 inhibitors(DPP-4i)have an important place in the management of type 2 diabetes.The DPP-4 enzyme is ubiquitously distributed throughout the human body and has multiple substrates through which it regulates several important physiological functions.DPP-4 regulates several immune functions,including T-cell activation,macrophage function,and secretion of cytokines.Studies have reported an increase in autoimmune diseases like bullous pemphigoid,inflammatory bowel disease,and arthritis with DPP-4i use.The relationship of DPP-4i and autoimmune diseases is a complex one and warrants further research into the effect of DPP-4 inhibition on the immune system to understand the pathogenesis more clearly.Whether a particular cluster of autoimmune diseases is associated with DPP-4i use remains an important contentious issue.Nevertheless,a heightened awareness from the clinicians is required to identify and treat any such diseases.Through this review,we explore the clinical and pathophysiological characteristics of this association in light of recent evidence. 展开更多
关键词 Autoimmune disease Bullous pemphigoid Diabetes Dipeptidyl peptidase-4 inhibitors Gliptins Inflammation
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Review on the Effect of Glucagon-Like Peptide-1 Receptor Agonists and Dipeptidyl Peptidase-4 Inhibitors for the Treatment of Non-Alcoholic Fatty Liver Disease 认领 引用 被引量：3
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作者 李超林 赵璐杰 +2 位作者 周新丽 吴慧潇 赵家军 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 2015年第3期333-336,共4页
Non-alcoholic fatty liver disease（NAFLD） is a common liver disease and it represents the hepatic manifestation of metabolic syndrome, which includes type 2 diabetes mellitus（T2DM）, dyslipidemia, central obesity an... Non-alcoholic fatty liver disease（NAFLD） is a common liver disease and it represents the hepatic manifestation of metabolic syndrome, which includes type 2 diabetes mellitus（T2DM）, dyslipidemia, central obesity and hypertension. Glucagon-like peptide-1（GLP-1） analogues and dipeptidyl peptidase-4（DPP-4） inhibitors were widely used to treat T2 DM. These agents improve glycemic control, promote weight loss and improve lipid metabolism. Recent studies have demonstrated that the GLP-1 receptor（GLP-1R） is present and functional in human and rat hepatocytes. In this review, we present data from animal researches and human clinical studies that showed GLP-1 analogues and DPP-4 inhibitors can decrease hepatic triglyceride（TG） content and improve hepatic steatosis, although some effects could be a result of improvements in metabolic parameters. Multiple hepatocyte signal transduction pathways and m RNA from key enzymes in fatty acid metabolism appear to be activated by GLP-1 and its analogues. Thus, the data support the need for more rigorous prospective clinical trials to further investigate the potential of incretin therapies to treat patients with NAFLD. 展开更多
关键词 glucagon-like peptide-1 receptor agonists dipeptidyl peptidase-4 non-alcoholic fatty liverdisease insulin resistance type 2 diabetes mellitus
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Macrophage modulation with dipeptidyl peptidase-4 inhibitors:A new frontier for treating diabetic cardiomyopathy? 认领 引用 被引量：2
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作者 Saeed Mohammadi Ahmed Al-Harrasi 《World Journal of Diabetes》 SCIE 2024年第9期1847-1852,共6页
This editorial introduces the potential of targeting macrophage function for diabetic cardiomyopathy(DCM)treatment by dipeptidyl peptidase-4(DPP-4)inhibitors.Zhang et al studied teneligliptin,a DPP-4 inhibitor used fo... This editorial introduces the potential of targeting macrophage function for diabetic cardiomyopathy(DCM)treatment by dipeptidyl peptidase-4(DPP-4)inhibitors.Zhang et al studied teneligliptin,a DPP-4 inhibitor used for diabetes management,and its potential cardioprotective effects in a diabetic mouse model.They suggested teneligliptin administration may reverse established markers of DCM,including cardiac hypertrophy and compromised function.It also inhibited the NLRP3 inflammasome and reduced inflammatory cytokine production in diabetic mice.Macrophages play crucial roles in DCM pathogenesis.Chronic hyperglycemia disturbs the balance between pro-inflammatory(M1)and antiinflammatory(M2)macrophages,favoring a pro-inflammatory state contributing to heart damage.Here,we highlight the potential of DPP-4 inhibitors to modulate macrophage function and promote an anti-inflammatory environment.These compounds may achieve this by elevating glucagon-like peptide-1 levels and potentially inhibiting the NLRP3 inflammasome.Further studies on teneligliptin in combination with other therapies targeting different aspects of DCM could be suggested for developing more effective treatment strategies to improve cardiovascular health in diabetic patients. 展开更多
关键词 Diabetic cardiomyopathy Macrophage Dipeptidyl peptidase-4 inhibitor Teneligliptin NLRP3 inflammasome Glucagon-like peptide-1
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Efficacy of omarigliptin,once-weekly dipeptidyl peptidase-4 inhibitor,in patients with type 2 diabetes 认领 引用
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作者 Eiji Kawasaki Yuko Nakano +6 位作者 Takahiro Fukuyama Aira Uchida Yoko Sagara Hidekazu Tamai Masayuki Tojikubo Yuji Hiromatsu Nobuhiko Koga 《World Journal of Diabetes》 SCIE 2021年第12期2087-2095,共9页
BACKGROUND Omarigliptin is one of several once-weekly dipeptidyl peptidase-4 inhibitors(DPP-4is).Despite the high frequency of switching from various daily DPP-4is to omarigliptin in actual clinical practice,data rega... BACKGROUND Omarigliptin is one of several once-weekly dipeptidyl peptidase-4 inhibitors(DPP-4is).Despite the high frequency of switching from various daily DPP-4is to omarigliptin in actual clinical practice,data regarding its efficacy in patients with type 2 diabetes(T2D)after switching are limited.AIM To analyze the efficacy of omarigliptin in Japanese patients with T2D who had previously received treatment with other glucose-lowering agents.METHODS Forty-nine T2D patients treated for the first time with omarigliptin were recruited retrospectively and divided into four groups defined as either add-on or switched from daily DPP-4is:switched from linagliptin,switched from sitagliptin,and switched from vildagliptin.During a 3-mo follow-up,the clinical parameters among these groups were assessed and compared,with the impact of the switch on glycemic variability as measured by continuous glucose monitoring also being evaluated in the switched groups.RESULTS Hemoglobin A1c levels saw a significant decrease of-0.32%±0.41%in the add-on group(P=0.002).However,the other groups’variables depended on the preswitch daily DPP-4i:switched from linagliptin,-0.05%±0.22%;switched from sitagliptin,-0.17%±0.33%;and switched from vildagliptin,0.45%±0.42%,which saw significant worsening(P=0.0007).Multivariate logistic regression analysis revealed that switching from vildagliptin to omarigliptin was independently associated with worsening glycemic control(P=0.0013).The mean and standard deviation of sensor glucose value,the mean amplitude of glycemic excursions,and the mean of daily difference significantly improved when switching the patient from either linagliptin or sitagliptin to omarigliptin.However,in patients switched from vildagliptin,not only did the glucose variability indices see no improvements,the mean of daily difference even underwent significant worsening.CONCLUSION Administering omarigliptin as add-on therapy or switching to it from sitagliptin and linagliptin,but not vildagliptin,improves glycemic control and thus should help in decision making when selecting DPP-4is for T2D patients. 展开更多
关键词 Omarigliptin Once-weekly dipeptidyl peptidase-4 inhibitor Real-world practice Retrospective study Type 2 diabetes
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Association between plasma dipeptidyl peptidase-4 levels and cognitive function in perinatal pregnant women with gestational diabetes mellitus 认领 引用 被引量：1
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作者 Si-Ri-Gu-Leng Sana En-You Li +1 位作者 Xi-Jin Deng Lei Guo 《World Journal of Clinical Cases》 SCIE 2021年第33期10161-10171,共11页
BACKGROUND Dipeptidyl peptidase-4(DPP4)is associated with cognitive dysfunction in patients with type 2 diabetes.AIM To assess a possible relationship between serum DPP4 and cognitive function in perinatal pregnant wo... BACKGROUND Dipeptidyl peptidase-4(DPP4)is associated with cognitive dysfunction in patients with type 2 diabetes.AIM To assess a possible relationship between serum DPP4 and cognitive function in perinatal pregnant women with gestational diabetes mellitus(GDM).METHODS The study subjects were divided into three groups:GDM group(n=81),healthy pregnant(HP)group(n=85),and control group(n=51).The Montreal Cognitive Assessment(MoCA)was used to assess the cognitive status of each group.Venous blood samples were collected to measure blood lipids,glycated hemoglobin,and glucose levels.For each participant,a 3-mL blood sample was collected and centrifuged,and the serum was collected.Blood samples were stored at-80℃,and DPP4,interleukin-6(IL-6),and 8-iso-prostaglandin F2α(8-iso-PGF2α),and brain-derived neurotrophic factor(BDNF)were detected using ELISA.RESULTS The MoCA scores in the GDM and HP groups were significantly different from those in the control group in terms of visuospatial/executive function and attention(P0.05).In terms of language,the GDM group had significantly different scores from those in the other two groups(P0.05).The level of BDNF in the GDM group was significantly lower than that in the HP and control groups(P0.05).CONCLUSION Cognitive dysfunction in perinatal pregnant women with GDM mainly manifested as memory loss,which might be associated with elevated DPP4 levels. 展开更多
关键词 Gestational diabetes mellitus Dipeptidyl peptidase-4 Cognitive function Oxidative stress Perinatal pregnant women Montreal cognitive assessment
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Neuroprotection by dipeptidyl-peptidase-4 inhibitors and glucagonlike peptide-1 analogs via the modulation of AKT-signaling pathway in Alzheimer’s disease 认领 引用 被引量：3
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作者 Yuka Ikeda Nozomi Nagase +2 位作者 Ai Tsuji Yasuko Kitagishi Satoru Matsuda 《World Journal of Biological Chemistry》 2021年第6期104-113,共10页
Alzheimer’s disease(AD)is the most common reason for progressive dementia in the elderly.It has been shown that disorders of the mammalian/mechanistic target of rapamycin(mTOR)signaling pathways are related to the AD... Alzheimer’s disease(AD)is the most common reason for progressive dementia in the elderly.It has been shown that disorders of the mammalian/mechanistic target of rapamycin(mTOR)signaling pathways are related to the AD.On the other hand,diabetes mellitus(DM)is a risk factor for the cognitive dysfunction.The pathogenesis of the neuronal impairment caused by diabetic hyperglycemia is intricate,which contains neuro-inflammation and/or neurodegeneration and dementia.Glucagon-like peptide-1(GLP1)is interesting as a possible link between metabolism and brain impairment.Modulation of GLP1 activity can influence amyloid-beta peptide aggregation via the phosphoinositide-3 kinase/AKT/mTOR signaling pathway in AD.The GLP1 receptor agonists have been shown to have favorable actions on the brain such as the improvement of neurological deficit.They might also exert a beneficial effect with refining learning and memory on the cognitive impairment induced by diabetes.Recent experimental and clinical evidence indicates that dipeptidyl-peptidase-4(DPP4)inhibitors,being currently used for DM therapy,may also be effective for AD treatment.The DPP-4 inhibitors have demonstrated neuroprotection and cognitive improvements in animal models.Although further studies for mTOR,GLP1,and DPP4 signaling pathways in humans would be intensively required,they seem to be a promising approach for innovative AD-treatments.We would like to review the characteristics of AD pathogenesis,the key roles of mTOR in AD and the preventive and/or therapeutic suggestions of directing the mTOR signaling pathway. 展开更多
关键词 Alzheimer’s disease Cognitive disorder Dementia Glucagon-like peptide-1 Dipeptidyl peptidase-4 Mammalian/mechanistic target of rapamycin
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Risk of pancreatic adverse events associated with the use of glucagon-like peptide-1 receptor agonist and dipeptidyl peptidase-4 inhibitor drugs: A systematic review and metaanalysis of randomized trials 认领 引用 被引量：1
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作者 Hasan M Shihab Tokunbo Akande +2 位作者 Kacie Armstrong Sonal Singh Yoon K Loke 《World Journal of Meta-Analysis》 2015年第6期254-283,共30页
AIM: To systematically assess risk of pancreatic adverse events with glucagon-like peptide-1(GLP-1) receptor agonist and dipeptidyl peptidase-4(DPP-4) inhibitor drugs.METHODS: We searched Pub Med, Embase, CINAHL, Coch... AIM: To systematically assess risk of pancreatic adverse events with glucagon-like peptide-1(GLP-1) receptor agonist and dipeptidyl peptidase-4(DPP-4) inhibitor drugs.METHODS: We searched Pub Med, Embase, CINAHL, Cochrane review of clinical trials, pharmaceutical company clinical trials register, United States Food and Drug Administration website, European Medicines Agency website and Clinical Trials.gov for randomized controlled trials from inception to October 2013. Randomized control trial studies were selected for inclusion if they reported on pancreatic complication events and/or changes in pancreatic enzyme levels(serum amylase and serum lipase) as adverse events or as serious adverse events for patients who were on GLP-1 receptor agonist and DPP-4 inhibitor drugs. Two independent reviewers extracted data directly. We performed Peto odds ratio(OR) fixed effect meta-analysis of pancreatic adverse events a, and assessed heterogeneity with the I^2 statistic.RESULTS: Sixty-eight randomized controlled trials were eligible. A total of 60720 patients were included in our analysis of the association of risk of pancreatic complication events with GLP-1 agents. A total of 89 pancreatic related adverse events occurred among the GLP-1 agents compared to 74 events among the controls. There was a statistically significant increased risk of elevation of pancreatic enzymes associated with GLP-1 agents compared with control(Peto OR = 3.15, 95%CI: 1.56-6.39, P = 0.001, I2 = 0%). There was no statistically significant difference in the risk of pancreatic adverse event associated with GLP-1 agent compared with controls(Peto OR = 1.00, 95%CI: 0.73-1.37, P = 1.00, I2 = 0%). There were a total of 71 pancreatitis events in patients on GLP-1 agents and 56 pancreatitis events occurred in the control patients. There were 36 reports of pancreatic cancer in these studies. Of these cases, 2 used linagliptin, 2 used alogliptin, 1 used vildagliptin, 7 used saxagliptin while 6 used sitagliptin. The remaining 18 cases occurred among controls.CONCLUSION: Although GLP-1 based agents are associated with pancreatic enzyme elevation, we were unable to confirm a significant risk of pancreatitis or pancreatic cancer. 展开更多
关键词 Diabetes mellitus Pancreatitis Glucagon-like peptide-1 agonists Dipeptidyl peptidase-4 inhibitors Meta-analysis
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Diabetes therapies in hemodialysis patients: Dipeptidase-4 inhibitors 认领 引用 被引量：1
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作者 Yuya Nakamura Hitomi Hasegawa +8 位作者 Mayumi Tsuji Yuko Udaka Masatomo Mihara Tatsuo Shimizu Michiyasu Inoue Yoshikazu Goto Hiromichi Gotoh Masahiro Inagaki Katsuji Oguchi 《World Journal of Diabetes》 2015年第6期840-849,共10页
Although several previous studies have been published on the effects of dipeptidase-4(DPP-4) inhibitors in diabetic hemodialysis(HD) patients, the findings have yet to be reviewed comprehensively. Eyesight failure cau... Although several previous studies have been published on the effects of dipeptidase-4(DPP-4) inhibitors in diabetic hemodialysis(HD) patients, the findings have yet to be reviewed comprehensively. Eyesight failure caused by diabetic retinopathy and aging-related dementia make multiple daily insulin injections difficult for HD patients. Therefore, we reviewed the effects of DPP-4 inhibitors with a focus on oral antidiabetic drugs as a new treatment strategy in HD patients with diabetes. The following 7 DPP-4 inhibitors are available worldwide: sitagliptin, vildagliptin, alogliptin, linagliptin, teneligliptin, anagliptin, and saxagliptin. All of these are administered once daily with dose adjustments in HD patients. Four types of oral antidiabetic drugs can be administered for combination oral therapy with DPP-4 inhibitors, including sulfonylureas, meglitinide, thiazolidinediones, and alpha-glucosidase inhibitor. Nine studies examined the antidiabetic effects in HD patients. Treatments decreased hemoglobin A1 c and glycated albumin levels by 0.3% to 1.3% and 1.7% to 4.9%, respectively. The efficacy of DPP-4 inhibitor treatment is high among HD patients, and no patients exhibited significant severe adverse effects such as hypoglycemia and liver dysfunction. DPP-4 inhibitors are key drugs in new treatment strategies for HD patients with diabetes and with limited choices for diabetes treatment. 展开更多
关键词 Dipeptidase-4 inhibitors Hemodialysis Diabetes mellitus Blood glucose-related factors Antiinflammatoryeffects
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Peroxisome proliferator-activated receptor-alpha activation and dipeptidyl peptidase-4 inhibition target dysbiosis to treat fatty liver in obese mice 认领 引用 被引量：5
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作者 Flavia Maria Silva-Veiga Carolline Santos Miranda +4 位作者 Isabela Macedo Lopes Vasques-Monteiro Henrique Souza-Tavares Fabiane Ferreira Martins Julio Beltrame Daleprane Vanessa Souza-Mello 《World Journal of Gastroenterology》 SCIE CAS 2022年第17期1814-1829,共16页
BACKGROUND Obesity and comorbidities onset encompass gut dysbiosis,altered intestinal permeability,and endotoxemia.Treatments that target gut dysbiosis can cope with obesity and nonalcoholic fatty liver disease(NAFLD)... BACKGROUND Obesity and comorbidities onset encompass gut dysbiosis,altered intestinal permeability,and endotoxemia.Treatments that target gut dysbiosis can cope with obesity and nonalcoholic fatty liver disease(NAFLD)management.Peroxisome proliferator-activated receptor(PPAR)-alpha activation and dipeptidyl-peptidase-4(DPP-4)inhibition alleviate NAFLD,but the mechanism may involve gut microbiota modulation and merits further investigation.AIM To address the effects of PPAR-alpha activation and DPP-4 inhibition(isolated or combined)upon the gut-liver axis,emphasizing inflammatory pathways in NAFLD management in high-fat-fed C57BL/6J mice.METHODS Male C57BL/6J mice were fed a control diet(C,10%of energy as lipids)or a highfat diet(HFD,50%of energy as lipids)for 12 wk,when treatments started,forming the groups:C,HF,HFA(HFD+PPAR-alpha agonist WY14643,2.5 mg/kg body mass),HFL(HFD+DPP-4 inhibitor linagliptin,15 mg/kg body mass),and HFC(HFD+the combination of WY14643 and linagliptin).RESULTS The HFD was obesogenic compared to the C diet.All treatments elicited significant body mass loss,and the HFC group showed similar body mass to the C group.All treatments tackled oral glucose intolerance and raised plasma glucagon-like peptide-1 concentrations.These metabolic benefits restored Bacteroidetes/Firmicutes ratio,resulting in increased goblet cells per area of the large intestine and reduced lipopolysaccharides concentrations in treated groups.At the gene level,treated groups showed higher intestinal Mucin 2,Occludin,and Zo-1 expression than the HFD group.The reduced endotoxemia suppressed inflammasome and macrophage gene expression in the liver of treated animals.These observations complied with the mitigation of liver steatosis and reduced hepatic triacylglycerol,reassuring the role of the proposed treatments on NAFLD mitigation.CONCLUSION PPAR alpha activation and DPP-4 inhibition(isolated or combined)tackled NAFLD in dietinduced obese mice by restoration of gut-liver axis.The reestablishment of the intestinal barrier and the rescued phylogenetic gut bacteria distribution mitigated liver steatosis through antiinflammatory signals.These results can cope with NAFLD management by providing pre-clinical evidence that drugs used to treat obesity comorbidities can help to alleviate this silent and harmful liver disease. 展开更多
关键词 Nonalcoholic fatty liver disease High-fat diet Peroxisome proliferator-activated receptor-alpha Dipeptidyl-peptidase-4-inhibitor Dysbiosis Inflammation
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Synthesis and biological evaluation of piperazine derivatives on dipeptidyl peptidase-4 认领 引用 被引量：2
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作者 孟祥国 蔡正艳 +1 位作者 张伟 周伟澄 《Journal of Chinese Pharmaceutical Sciences》 CAS CSCD 2013年第2期167-172,共6页
A series of （4-（2,4,5-trifluorophenyl）piperazin-1-yl） methanone derivatives 9a–k as potential dipeptidyl peptidase-4 （DPP-4） inhibitors were synthesized by microwave assisted nucleophilic substitution of 1,2,4,... A series of （4-（2,4,5-trifluorophenyl）piperazin-1-yl） methanone derivatives 9a–k as potential dipeptidyl peptidase-4 （DPP-4） inhibitors were synthesized by microwave assisted nucleophilic substitution of 1,2,4,5-tetrafluorobenzene with piperazine, followed by carbamoylation and condensation. The inhibitory activities of these new compounds on DPP-4 were evaluated in vitro, and compounds 9d and 9g showed moderate inhibitory activities. 展开更多
关键词 DPP-4 DPP-4 inhibitor Derivative Synthesize
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No significant association between dipeptidyl peptidase-4 inhibitors and adverse outcomes of COVID-19 认领 引用 被引量：1
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作者 Jiang-Hua Zhou Bin Wu +13 位作者 Wen-Xin Wang Fang Lei Xu Cheng Juan-Juan Qin Jing-Jing Cai Xiao-Jing Zhang Feng Zhou Ye-Mao Liu Hao-Miao Li Li-Hua Zhu Zhi-Gang She Xin Zhang Juan Yang Hong-Liang Li 《World Journal of Clinical Cases》 SCIE 2020年第22期5576-5588,共13页
BACKGROUND Dipeptidyl peptidase-4(DPP4)is commonly targeted to achieve glycemic control and has potent anti-inflammatory and immunoregulatory effects.Recent structural analyses indicated a potential tight interaction ... BACKGROUND Dipeptidyl peptidase-4(DPP4)is commonly targeted to achieve glycemic control and has potent anti-inflammatory and immunoregulatory effects.Recent structural analyses indicated a potential tight interaction between DPP4 and severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),raising a promising hypothesis that DPP4 inhibitor(DPP4i)drugs might be an optimal strategy for treating coronavirus disease 2019(COVID-19)among patients with diabetes.However,there has been no direct clinical evidence illuminating the associations between DPP4i use and COVID-19 outcomes.AIM To illuminate the associations between DPP4i usage and the adverse outcomes of COVID-19.METHODS We conducted a multicenter,retrospective analysis including 2563 patients with type 2 diabetes who were hospitalized due to COVID-19 at 16 hospitals in Hubei Province,China.After excluding ineligible individuals,142 patients who received DPP4i drugs and 1115 patients who received non-DPP4i oral anti-diabetic drugs were included in the subsequent analysis.We performed a strict propensity score matching(PSM)analysis where age,sex,comorbidities,number of oral hypoglycemic agents,heart rate,blood pressure,pulse oxygen saturation(SpO2)<95%,CT diagnosed bilateral lung lesions,laboratory indicators,and proportion of insulin usage were matched.Finally,111 participants treated with DPP4i drugs were successfully matched to 333 non-DPP4i users.Then,a linear logistic model and mixed-effect Cox model were applied to analyze the associations between inhospital DPP4i use and adverse outcomes of COVID-19.RESULTS After rigorous matching and further adjustments for imbalanced variables in the linear logistic model and Cox adjusted model,we found that there was no significant association between in-hospital DPP4i use(DPP4i group)and 28-d allcause mortality(adjusted hazard ratio=0.44,95%CI:0.09-2.11,P=0.31).Likewise,the incidences and risks of secondary outcomes,including septic shock,acute respiratory distress syndrome,or acute organ(kidney,liver,and cardiac)injuries,were also comparable between the DPP4i and non-DPP4i groups.The performance of DPP4i agents in achieving glucose control(e.g.,the median level of fasting blood glucose and random blood glucose)and inflammatory regulation was approximately equivalent in the DPP4i and non-DPP4i groups.Furthermore,we did not observe substantial side effects such as uncontrolled glycemia or acidosis due to DPP4i application relative to the use of non-DPP4i agents in the study cohort.CONCLUSION Our findings demonstrated that DPP4i use is not significantly associated with poor outcomes of COVID-19 or other adverse effects of anti-diabetic treatment.The data support the continuation of DPP4i agents for diabetes management in the setting of COVID-19. 展开更多
关键词 COVID-19 SARS-CoV-2 DPP4 inhibitors Diabetes Glucose control Adverse effects
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Repositioning of dipeptidyl peptidase-4 inhibitors and glucagon like peptide-1 agonists as potential neuroprotective agents 认领 引用 被引量：6
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作者 Shaker A.Mousa Bassam M.Ayoub 《Neural Regeneration Research》 SCIE CAS CSCD 2019年第5期745-748,共4页
Repositioning of dipeptidyl peptidase-4 inhibitors and glucagon like peptide-1 receptor agonists is a breakthrough in the field of neural regeneration research increasing glucagon like peptide-1 bioavailability, hence... Repositioning of dipeptidyl peptidase-4 inhibitors and glucagon like peptide-1 receptor agonists is a breakthrough in the field of neural regeneration research increasing glucagon like peptide-1 bioavailability, hence its neuroprotective activities. In this article, the authors suggest not only crossing blood-brain barrier and neurodegenerative disease as off target for dipeptidyl peptidase-4 inhibitors and glucagon like peptide-1 receptor agonists, but also for ophthalmic preparations for diabetic retinopathy, which may be the latest breakthrough in the field if prepared and used in an appropriate nano-formulation to target the retinal nerves. The relation of neurodegenerative diseases' different mechanisms to the dipeptidyl peptidase-4 inhibitors and glucagon like peptide-1 receptor agonists should be further examined in preclinical and clinical settings. The repositioning of already marketed antidiabetic drugs for neurodegenerative diseases should save the high cost of the time-consuming normal drug development process. Drug repositioning is a hot topic as an alternative to molecular target based drug discovery or therapeutic switching. It is a relatively inexpensive pathway due to availability of previous pharmacological and safety data. The glucagon like peptide-1 produced in brain has been linked to enhanced learning and memory functions as a physiologic regulator in central nervous system by restoring insulin signaling. Intranasal administration of all marketed gliptins(or glucagon like peptide-1 receptor agonists) may show enhanced blood-brain barrier crossing and increased glucagon like peptide-1 levels in the brain after direct crossing of the drug for the olfactory region, targeting the cerebrospinal fluid. Further blood-brain barrier crossing tests may extend dipeptidyl peptidase-4 inhibitors' effects beyond the anti-hyperglycemic control to intranasal spray, intranasal powder, or drops targeting the blood-brain barrier and neurodegenerative diseases with the most suitable formula. Moreover, novel nano-formulation is encouraged either to obtain favorable pharmacokinetic parameters or to achieve promising blood-brain barrier penetration directly through the olfactory region. Many surfactants should be investigated either as a solubilizing agent for hydrophobic drugs or as penetration enhancers. Different formulae based on in vitro and in vivo characterizations, working on sister gliptins(or glucagon like peptide-1 receptor agonists), different routes of administration, pharmacokinetic studies, dose response relationship studies, monitoring of plasma/brain concentration ratio after single and multiple dose, and neurodegenerative disease animal models are required to prove the new method of use(utility) for dipeptidyl peptidase-4 inhibitors as potential neuroprotective agents. Furthermore, investigations of glucagon like peptide-1 receptor agonists' neuroprotective effects on animal models will be considered carefully because they crossed the blood-brain barrier in previous studies, enabling their direct action on the central nervous system. Combination therapy of dipeptidyl peptidase-4 inhibitors or glucagon like peptide-1 receptor agonists with already marketed drugs for neurodegenerative disease should be considered, especially regarding the novel intranasal route of administration. 展开更多
关键词 repositioning DPP-4 inhibitors GLP-1RA neural regeneration blood-brain barrier Parkinson’s disease Alzheimer’s disease diabetic retinopathy
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Antihyperglycaemic activity of ethylacetate extract of Chlorophytum alismifolium in type 2 diabetes:The involvement of peroxisome proliferator-activated receptor-γand dipeptidyl peptidase-4 认领 引用 被引量：3
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作者 Abdulhakim Abubakar Abdullahi Balarabe Nazifi +3 位作者 Idris Mohammed Maje Yusuf Tanko Joseph Akpojo Anuka Ezzeldin Mukthar Abdurahman 《Journal of Integrative Medicine》 SCIE CAS CSCD 2021年第1期78-84,共7页
Objective:This research is to investigate the antihyperglycaemic activity and the underlying mechanisms of action of the ethylacetate extract of Chlorophytum alismifolium(EACA)tubers in a type 2 diabetes model.Methods... Objective:This research is to investigate the antihyperglycaemic activity and the underlying mechanisms of action of the ethylacetate extract of Chlorophytum alismifolium(EACA)tubers in a type 2 diabetes model.Methods:The tubers were processed and sequentially extracted in hexane followed by ethylacetate,using a Soxhlet apparatus,and subjected to gas chromatography-mass spectrometry(GC–MS).The acute toxicity of EACA was investigated in albino Wistar rats.An antihyperglycaemic study was carried out using high-fat diet(pelletized diet and margarine in the ratio of 10:1 and 20%fructose solution)and streptozotocin-induced hyperglycaemic Wistar rats.The effects of the extract(150,300 and 600 mg/kg)on blood glucose level,insulin,peroxisome proliferator-activated receptor-c(PPAR-c)and dipeptidyl peptidase-4(DPP-4)were evaluated using enzyme-linked immunosorbent assay.Results:The oral median lethal dose in Wistar rats was estimated to be>5000 mg/kg.Treatment with EACA at all doses significantly reduced the fasting blood glucose levels,compared to the hyperglycaemic control,and over time.Administration of EACA increased the serum insulin and PPAR-c levels while decreasing DPP-4 levels.GC–MS analysis revealed the presence of 13 compounds,with isothiazole and isoxazolidine covering total area of 24.6%and 22.69%,respectively.Conclusion:The findings from this study showed that EACA has important compounds with beneficial effect in type 2 diabetes and acts by increasing insulin secretion and PPAR-c level and decreasing DPP-4 activity. 展开更多
关键词 Chlorophytum alismifolium Diabetes mellitus Gas chromatography-mass spectrometry Insulin Peroxisome proliferator-activated receptor-c Dipeptidyl-peptidase 4
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Dipeptidyl Peptidase-4 Inhibitors and Inflammation: Dpp-4 Inhibitors Improve Mean Pleatelet Volume and Gamma Glutamyl Transferase Level 认领 引用
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作者 Deniz Avci 《Journal of Biosciences and Medicines》 2019年第2期42-53,共12页
AIM: The purpose of this research was to determine the changes of the inflammatory parameters in the long term with the use of dipeptidyl peptidase-4 inhibitors. Material and Methods: In this research we have retrospe... AIM: The purpose of this research was to determine the changes of the inflammatory parameters in the long term with the use of dipeptidyl peptidase-4 inhibitors. Material and Methods: In this research we have retrospectively reviewed the records of 80 patients who had added dipeptidyl peptidase-4 inhibitors (40 sitagliptin and 40 vildagliptin) to their ongoing therapies. Patients’ values of inflammation at the beginning of this process were taken as initial values, while values at the end of this process were considered as final values. Results: A total of 80 patients [38.8% (n = 31) of the patients were male, while 61.3% (n = 49) were female] enrolled in the study. When the whole group was evaluated, the mean age was 56.1 ± 9.7 years. The median follow-up time of the patients with DPP-4 inhibitors was 18 (2 - 64) months. The mean MPV value was measured as 8.79 ± 1.71 fL before DPP-4 inhibitors and it was 10.06 ± 1.42 fL after the follow-up period (p < 0.001). The median value serum GGT was 30.5 (13 - 194) U/L before DPP-4 inhibitor and 29.5 (12 - 112) U/L at the end (p = 0.048). The mean uric acid level before the use of di-peptidyl peptidase-4 inhibitors was 4.7 ± 1.6 mg/dL, and this level was 5.0 ± 1.5 mg/dL after the follow-up period (p = 0.048). Conclusion: In this study, it was observed that MPV and GGT levels were improved by dipeptidyl peptidase-4 inhibitors in long-term. 展开更多
关键词 DPP-4 Inhibitors MPV GGT Inflammation Diabetes Mellitus
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基于TLR-4/MyD88/NF-κB信号通路探究温针灸干预膝骨关节炎的作用机制 认领 引用 被引量：4
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作者 王树东 董宝强 +5 位作者 盛泽伟 胡哲 于冬冬 王列 丁学峰 薛亚楠 《中华中医药学刊》 CAS CSCD 北大核心 2026年第2期24-27,I0008-I0012,共4页
目的基于Toll样受体-4(Toll-like receptors 4,TLR-4)/髓样分化因子88(Myeloid differentiation factor 88,MyD88)/核转录因子-κB(Nuclear transcription factor-kappa B,NF-κB)信号通路观察温针灸对膝骨关节炎(Knee osteoarthritis,K... 目的基于Toll样受体-4(Toll-like receptors 4,TLR-4)/髓样分化因子88(Myeloid differentiation factor 88,MyD88)/核转录因子-κB(Nuclear transcription factor-kappa B,NF-κB)信号通路观察温针灸对膝骨关节炎(Knee osteoarthritis,KOA)家兔模型的调控作用,探讨温针灸治疗膝骨关节炎的作用机制。方法健康大耳白兔40只,随机分为空白组、模型组、温针灸组、西药组,每组10只,以改良Hulth法建立膝骨关节炎模型,经4周干预后,随机处死两只,病理检查出现关节软骨表面不平整、炎性细胞浸润等改变即表明造模成功。采用HE染色法观察家兔膝关节形态学变化并进行光镜软骨检测评价标准(Mankin score,Mankin’s)评分;采用免疫组化法观察家兔膝关节软骨组织TLR-4、MyD88、NF-κB的表达,并进行半定量分析;采用酶联免疫吸附(Enzyme-linked immunosorbent assay,ELISA)法检测家兔血清中白细胞介素-6(Interleukin-6,IL-6)、白细胞介素-1β(Interleukin-1β,IL-1β)、肿瘤坏死因子-α(Tumor necrosis factor-α,TNF-α)的含量;采用Wes全自动蛋白质印迹定量分析系统检测软骨组织TLR-4、MyD88、NF-κB的蛋白表达水平。结果HE染色可见空白组家兔膝关节软骨组织平整,无任何病理变化。模型组软骨组织表面粗糙,软骨细胞呈簇状堆积或减少。温针灸组以及西药组软骨组织表面欠平整,少量裂隙,伴有少量炎性细胞浸润。与空白组相比,模型组血清中IL-6、IL-1β、TNF-α含量显著升高(P<0.05),与模型组相比,温针灸组和西药组血清中IL-6、IL-1β、TNF-α含量显著下降(P<0.05);与空白组相比,模型组软骨组织TLR-4、MyD88、NF-κB蛋白表达显著升高(P<0.05),与模型组相比,温针灸组和西药组软骨组织TLR-4、MyD88、NF-κB蛋白表达显著下降(P<0.05),且温针灸组效果更为显著。结论温针灸可以通过抑制TLR-4/MyD88/NF-κB信号通路被激活,减少下游IL-6、IL-1β、TNF-α的含量以缓解炎症反应,延缓病程进展,达到治疗KOA的目的,并能够对软骨组织起到一定程度的修复作用。 展开更多
关键词 膝骨关节炎 温针灸 炎症反应 TLR-4 MyD88 NF-κB
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MOF衍生的g-C3N4/ZnIn2S4 S型异质结:界面工程增强光催化NO转化 认领 引用 被引量：1
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作者 邱艳平 张佳桐 +3 位作者 李林萍 高旸钦 李宁 戈磊 《物理化学学报》 SCIE CAS CSCD 北大核心 2026年第4期121-136,共16页
为应对大气中日益严峻的氮氧化物(NOx)污染问题,亟需开发兼具高效性与高选择性的光催化剂。本研究构建了g-C3N4/ZnIn2S4(CN/ZIS)S型异质结光催化剂,其中通过MOF衍生策略合成了具有中空管状形貌的ZnIn2S4,g-C3N_(4... 为应对大气中日益严峻的氮氧化物(NOx)污染问题,亟需开发兼具高效性与高选择性的光催化剂。本研究构建了g-C3N4/ZnIn2S4(CN/ZIS)S型异质结光催化剂,其中通过MOF衍生策略合成了具有中空管状形貌的ZnIn2S4,g-C3N4则作为高效电子转移平台。优化后的CN/ZIS-0.1在可见光照射下表现出显著提升的光催化性能,NO去除效率达67.29%,显著高于原始g-C3N4(41.41%)和ZIS(27.8%);同时NO向硝酸盐的选择性转化率达到77.47%,亦明显优于g-C3N4(49.01%)。材料表征结果表明,CN/ZIS-0.1不仅有更宽的光吸收范围,其独特结构还提供了更多反应位点。光电化学测试与DFT计算进一步证实,CN/ZIS界面形成的内建电场(BIEF)驱动光生电子向g-C3N4表面迁移、空穴向ZIS表面定向迁移,从而促进关键活性物种生成并增强NO吸附。本工作不仅证明了MOF衍生中空结构与二维半导体耦合构建S型异质结在NO光催化氧化中的潜力,还为开发高选择性NO光催化剂提供有效策略。 展开更多
关键词 光催化 NO转化 g-C3N4/ZnIn2S4异质结 界面工程 S型异质结
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茵陈蒿汤通过FXR抑制TLR4/MyD88/NF-κB信号通路改善胆汁淤积性肝损伤的机制 认领 引用 被引量：9
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作者 朱正望 杨洋 +6 位作者 赵静涵 王琳琳 唐银佩 蔡庆春 王兵 朱平生 苗明三 《中国实验方剂学杂志》 CAS CSCD 北大核心 2026年第1期47-54,共8页
目的:研究茵陈蒿汤通过调控法尼醇X受体(FXR)抑制Toll样受体4(TLR4)/髓样分化因子88(MyD88)/核转录因子-κB(NF-κB)信号通路改善胆汁淤积性肝损伤(CLI)的作用机制。方法Wistar雄性大鼠40只,随机选取10只为空白组,其余大鼠复制α-萘异... 目的:研究茵陈蒿汤通过调控法尼醇X受体(FXR)抑制Toll样受体4(TLR4)/髓样分化因子88(MyD88)/核转录因子-κB(NF-κB)信号通路改善胆汁淤积性肝损伤(CLI)的作用机制。方法Wistar雄性大鼠40只,随机选取10只为空白组,其余大鼠复制α-萘异硫氰酸酯(ANIT)诱导的CLI模型。造模后随机分为模型组、熊去氧胆酸组(0.1 g·kg-1)、茵陈蒿汤组(9.23 g·kg-1),每组10只,各给药组灌胃相应药物,连续3 d。检测血清中丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、碱性磷酸酶(ALP)、γ-谷氨酰转肽酶(γ-GT)、总胆汁酸(TBA)、总胆红素(TBil)、直接胆红素(DBil)水平;肝组织中肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-1β、IL-6水平;实时荧光定量聚合酶链式反应(Real-time PCR)检测肝组织中FXR、TLR4、MyD88、NF-κB、小鼠含生长因子样模体黏液样激素样受体(F4/80)、TNF-α、IL-1β、IL-6 mRNA表达;蛋白免疫印迹法(Western blot)检测肝组织中FXR、TLR4、MyD88、NF-κB蛋白表达;苏木素-伊红(HE)染色观察肝组织病理学变化。结果与空白组比较,模型组大鼠血清中ALT、AST、ALP、γ-GT、TBA、TBil、DBil水平显著升高(P<0.01),肝组织中TNF-α、IL-1β、IL-6水平及mRNA表达显著升高(P<0.01),肝组织中FXR mRNA及蛋白表达明显降低(P<0.05,P<0.01),TLR4、MyD88、NF-κB mRNA及蛋白表达、F4/80 mRNA表达显著升高(P<0.01);肝组织病理可见炎性细胞浸润、胆管上皮细胞增生性改变。与模型组比较,熊去氧胆酸组大鼠血清中ALT、ALP、γ-GT、TBA、TBil、DBil水平明显降低(P<0.05,P<0.01),肝组织中TNF-α、IL-1β、IL-6水平及mRNA表达明显降低(P<0.05,P<0.01),肝组织中TLR4、MyD88、NF-κB mRNA及蛋白表达、F4/80 mRNA表达明显降低(P<0.05,P<0.01);茵陈蒿汤组大鼠血清中ALT、AST、ALP、γ-GT、TBA、TBil、DBil水平明显降低(P<0.05,P<0.01),肝组织中TNF-α、IL-1β、IL-6水平及mRNA表达显著降低(P<0.01),肝组织中FXR mRNA及蛋白表达明显升高,TLR4、MyD88、NF-κB、F4/80 mRNA及TLR4、NF-κB蛋白表达明显降低(P<0.05,P<0.01);肝组织炎性细胞浸润减轻,胆管上皮细胞增生减少。结论茵陈蒿汤对CLI具有明显的保护作用,其机制可能与调控FXR抑制TLR4/MyD88/NF-κB通路介导的炎症反应有关。 展开更多
关键词 茵陈蒿汤 胆汁淤积 肝损伤 法尼醇X受体(FXR) Toll样受体4(TLR4)/髓样分化因子88(MyD88)/核转录因子-κB(NF-κB)信号通路
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