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1.
J Agric Food Chem ; 69(37): 10885-10892, 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34494818

RESUMO

Broccoli-derived peptides show beneficial metabolic effects, and it is necessary to examine their exact functional sequences. First, peptides from the trypsin hydrolysate of broccoli proteins were isolated and identified using column chromatography and quadrupole time-of-flight mass spectrometry. After that, their functions were verified by oral administration. The results identified two novel peptides as Leu-Pro-Gly-Val-Leu-Pro-Val-Ala (LPGVLPVA) and Tyr-Leu-Tyr-Ser-Pro-Ala-Tyr (YLYSPAY). LPGVLPVA exhibited an ACE IC50 value of 0.776 ± 0.03 µM and a DPP-IV IC50 value of 392 ± 24 µM; YLYSPAY showed an ACE IC50 value of 8.52 ± 0.63 µM and a DPP-IV IC50 value of 181 ± 4 µM. Administration of the peptides reduced the blood pressure of spontaneously hypertensive rats and reduced blood glucose levels in the oral glucose tolerance test in mice. The results indicated that LPGVLPVA and YLYSPAY could be potential nutritional candidates for hypertensive and diabetic people, especially for those with diabetes associated with hypertension.


Assuntos
Inibidores da Enzima Conversora de Angiotensina , Brassica , Inibidores da Dipeptidil Peptidase IV , Angiotensina I , Animais , Brassica/química , Camundongos , Peptídeos , Ratos , Tripsina
2.
Am J Manag Care ; 27(8): e269-e277, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34460181

RESUMO

OBJECTIVES: Using a US payer perspective, this study aimed to compare the lifetime cost-effectiveness of adding sodium-glucose cotransporter 2 (SGLT2) inhibitors vs switching to glucagon-like peptide 1 receptor agonists (GLP-1 RAs) among patients with type 2 diabetes who were not at glycated hemoglobin A1c target after dual therapy with metformin and dipeptidyl peptidase-4 (DPP-4) inhibitors. STUDY DESIGN: The cost-effectiveness analysis was performed with the validated IQVIA Core Diabetes Model. Treatment effects were obtained from randomized clinical trials with economic data based on published literature. METHODS: Risk of treatment-emergent adverse events and complications were simulated using submodels informed by published risk equations adjusted for patient characteristics, physiological parameters, and history of complications. Outcomes included cumulative incidence of micro- and macrovascular complications, life-years (LYs), quality-adjusted life-years (QALYs), and total costs. Scenario analyses were performed to assess robustness of results to variations in clinical and cost inputs and assumptions. RESULTS: Over a lifetime time horizon, adding an SGLT2 inhibitor dominated the strategy of switching to a GLP-1 RA, improving survival by 0.049 LYs and 0.026 QALYs, and was associated with cost savings of $9511. The majority of the scenario analyses confirmed dominance of the DPP-4 inhibitor + SGLT2 inhibitor pathway vs the GLP-1 RA pathway. The probabilistic sensitivity analysis reinforced the base-case finding of cost savings while gaining QALYs. CONCLUSIONS: Intensification with an SGLT2 inhibitor on top of a DPP-4 inhibitor demonstrated slightly better efficacy and cost savings compared with switching to a GLP-1 RA in patients not at glycemic goal with metformin and a DPP-4 inhibitor.


Assuntos
Diabetes Mellitus Tipo 2 , Inibidores da Dipeptidil Peptidase IV , Inibidores do Transportador 2 de Sódio-Glicose , Análise Custo-Benefício , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Hemoglobina A Glicada , Humanos , Hipoglicemiantes/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico
3.
Nutr Metab Cardiovasc Dis ; 31(10): 2945-2958, 2021 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-34420816

RESUMO

BACKGROUND AND AIMS: Studies of dipeptidyl peptidase inhibitors (DPP4is) report heterogeneous effects on cardiovascular targets in type 2 diabetes. This study aimed to investigate, in patients with impaired glucose tolerance (IGT), whether saxagliptin, a DPP4i, had beneficial cardiovascular effects at fasting and during the post-prandial state. METHODS AND RESULTS: In this randomized, placebo-controlled, double-blind, single-center pilot exploratory study, we included obese individuals with IGT. Twenty-four individuals (BMI 36.8 ± 4.8 kg/m2) were randomized to receive for 12 weeks either saxagliptin 5 mg a day or placebo. They were explored before and after a standardized breakfast for biological markers; microcirculatory blood flow at baseline and after transcutaneous administration of acetylcholine (Periflux System 5000® PERIMED); post-occlusive digital reactive hyperhemia (Endopat2000®); pulse wave velocity, augmentation index, central pulse pressure and subendocardial viability ratio (Sphygmocor®); cardiac hemodynamic parameters and cardiovascular autonomic nervous system activity (Task force monitor®). The results of all the investigations were similar after breakfast in the two groups at Visit 1 (acute post-prandial effects, after the first tablet) and Visit 2 (long-term post-prandial effects), and at fasting at Visit 1 and 2 (long-term effects, after 12 weeks of treatment). Only at Visit 2 the decrease in cardiac vagal activity occurring after breakfast was more sustained in the saxagliptin group than in the placebo group (interaction between treatment and time effect: p = 0.016). CONCLUSION: In obese patients with IGT, the effects of saxagliptin on the large set of cardiovascular parameters measured are neutral, except for a more marked post-prandial depression of vagal activity. CLINICAL TRIAL REGISTRATION NUMBER: NCT01521312.


Assuntos
Adamantano/análogos & derivados , Glicemia/efeitos dos fármacos , Sistema Cardiovascular/efeitos dos fármacos , Dipeptídeos/uso terapêutico , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Intolerância à Glucose/tratamento farmacológico , Obesidade/complicações , Período Pós-Prandial , Adamantano/efeitos adversos , Adamantano/uso terapêutico , Adulto , Biomarcadores/sangue , Glicemia/metabolismo , Sistema Cardiovascular/inervação , Sistema Cardiovascular/fisiopatologia , Dipeptídeos/efeitos adversos , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Método Duplo-Cego , Feminino , França , Intolerância à Glucose/sangue , Intolerância à Glucose/complicações , Intolerância à Glucose/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/fisiopatologia , Projetos Piloto , Fatores de Tempo , Resultado do Tratamento , Nervo Vago/efeitos dos fármacos , Nervo Vago/fisiopatologia
4.
Neurology ; 97(11): e1110-e1122, 2021 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-34380754

RESUMO

BACKGROUND AND OBJECTIVE: To investigate whether dipeptidyl peptidase-4 inhibitors (DPP-4i) have beneficial effects on amyloid aggregation and longitudinal cognitive outcome in diabetic Alzheimer disease-related cognitive impairment (ADCI). METHODS: We retrospectively reviewed 282 patients with ADCI with positive 18F-florbetaben amyloid PET images. Patients were classified into 3 groups according to prior diagnosis of diabetes and DPP-4i use: diabetic patients being treated with (ADCI-DPP-4i+, n = 70) or without DPP-4i (ADCI-DPP-4i-, n = 71) and nondiabetic patients (n = 141). Multiple linear regression analyses were performed to determine intergroup differences in global and regional amyloid retention using standardized uptake value ratios calculated from cortical areas. We assessed longitudinal changes in Mini-Mental State Examination (MMSE) score using a linear mixed model. RESULTS: The ADCI-DPP-4i+ group had lower global amyloid burden than the ADCI-DPP-4i- group (ß = 0.075, SE = 0.024, p = 0.002) and the nondiabetic ADCI group (ß = 0.054, SE = 0.021, p = 0.010) after adjusting for age, sex, education, cognitive status, and APOE ε4 carrier status. The ADCI-DPP-4i+ group had lower regional amyloid burden in temporo-parietal areas than either the ADCI-DPP-4i- group or the nondiabetic ADCI group. The ADCI-DPP-4i+ group showed a slower longitudinal decrease in MMSE score (ß = 0.772, SE = 0.272, p = 0.005) and memory recall subscore (ß = 0.291, SE = 0.116, p = 0.012) than the ADCI-DPP-4i- group. DISCUSSION: These findings suggest that DPP-4i use is associated with low amyloid burden and favorable long-term cognitive outcome in diabetic patients with ADCI.


Assuntos
Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/metabolismo , Disfunção Cognitiva/patologia , Complicações do Diabetes/patologia , Inibidores da Dipeptidil Peptidase IV/administração & dosagem , Hipoglicemiantes/administração & dosagem , Idoso , Doença de Alzheimer/complicações , Disfunção Cognitiva/complicações , Complicações do Diabetes/complicações , Complicações do Diabetes/tratamento farmacológico , Feminino , Humanos , Masculino , Fármacos Neuroprotetores/administração & dosagem , Estudos Retrospectivos , Resultado do Tratamento
5.
Life Sci ; 284: 119895, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34450166

RESUMO

AIMS: Dipeptidyl peptidase-4 inhibitor (DPP4i), a new antidiabetic agent, is reported to affect the progression of chronic liver diseases. The study aims to investigate the effects of DPP4i on contractile response, splanchnic hemodynamics, and portal pressure in cirrhotic rats. MATERIALS AND METHODS: A rat model of carbon tetrachloride-induced cirrhosis was used in this study. Sixteen rats with cirrhosis were treated with DDP4i sitagliptin for 5 consecutive days. Portal and systemic pressures and portal blood flow were measured. Mesenteric arterioles were isolated, and concentration-response curves to norepinephrine (NE) were evaluated. The expression of NADPH oxidase (Nox)1, Nox2, Nox4, and soluble epoxide hydrolase (sEH) were detected. Reactive oxygen species (ROS) and epoxyeicosatrienoic acid (EET) levels in mesenteric arteries were also measured. KEY FINDINGS: In cirrhotic rats, sitagliptin significantly reduced portal blood flow and portal pressure without effects on systemic pressure and reversed the decreased response of mesenteric arterioles to NE in an endothelium-dependent manner. Sitagliptin suppressed the increased Nox4 expression and ROS production. In vitro studies showed that Nox4 inhibitor enhanced arteriolar response to NE and reduced hydrogen peroxide (H2O2) level in cirrhotic rats. Sitagliptin also reduced EET levels and increased sEH expression of mesenteric vessels. Pre-incubation with sEH inhibitor in vitro reversed sitagliptin-induced augmentation of response to NE in cirrhotic rats. SIGNIFICANCE: DPP4 inhibition by sitagliptin in vivo has beneficial effects on portal hypertension in cirrhotic rats through normalizing arterial hypocontractility. DDP4 inhibitor may be a novel strategy in the treatment of patients with cirrhosis and portal hypertension.


Assuntos
Artérias/fisiopatologia , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Hipertensão Portal/complicações , Hipertensão Portal/tratamento farmacológico , Cirrose Hepática/complicações , Cirrose Hepática/fisiopatologia , Vasoconstrição , Animais , Artérias/efeitos dos fármacos , Inibidores da Dipeptidil Peptidase IV/farmacologia , Hemodinâmica/efeitos dos fármacos , Peróxido de Hidrogênio/metabolismo , Hipertensão Portal/fisiopatologia , Fígado/efeitos dos fármacos , Fígado/patologia , Cirrose Hepática/tratamento farmacológico , Masculino , Artérias Mesentéricas/efeitos dos fármacos , Artérias Mesentéricas/fisiopatologia , NADPH Oxidase 4/metabolismo , Norepinefrina/farmacologia , Ratos Sprague-Dawley , Fosfato de Sitagliptina/farmacologia , Regulação para Cima/efeitos dos fármacos , Vasoconstrição/efeitos dos fármacos
6.
Nutr Metab Cardiovasc Dis ; 31(10): 2745-2755, 2021 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-34364771

RESUMO

AIMS: Meta-analyses of randomized trials on Dipeptidyl Peptidase-4 inhibitors (DPP4i) reported discordant results on major cardiovascular events (MACE), mortality, and heart failure. Aim of this meta-analysis of randomized trials is the assessment of the cardiovascular safety of DPP4i. DATA SYNTHESIS: A Medline, Embase, Cochrane database search for sitagliptin, vildagliptin, omarigliptin, saxagliptin, alogliptin, trelagliptin, anagliptin, linagliptin, gemigliptin, evogliptin, and teneligliptin was performed up to up January 1st, 2020. All trials with a duration ≥24 weeks and comparing the effects of DPP4i with placebo or active drugs were collected. Mantel-Haenszel odds ratio (MH-OR) with 95% Confidence Interval (95% CI) was calculated for all outcomes defined above. A total of 182 eligible trials were identified. DPP-4i were not associated with an increased risk of MACE (MH-OR 0.99 [0.93, 1.04]), all-cause mortality (MH-OR 0.99 [0.93, 1.06]), and heart failure (MH-OR 1.05 [0.96, 1.15]) with no significant differences across individual molecules, except for saxagliptin, which was associated with an increased risk of heart failure. CONCLUSIONS: As a class, DPP4i are not associated with any increase or reduction of MACE, all-cause mortality, and heart failure. Saxagliptin seems to be associated with an increased risk of hospitalization for heart failure.


Assuntos
Adamantano/análogos & derivados , Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Dipeptídeos/uso terapêutico , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Adamantano/efeitos adversos , Adamantano/uso terapêutico , Idoso , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/mortalidade , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/mortalidade , Dipeptídeos/efeitos adversos , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Feminino , Fatores de Risco de Doenças Cardíacas , Insuficiência Cardíaca/induzido quimicamente , Insuficiência Cardíaca/epidemiologia , Hospitalização , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Fatores de Tempo , Resultado do Tratamento
8.
BMC Health Serv Res ; 21(1): 807, 2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34384428

RESUMO

BACKGROUND: Medicine purchasing in Chinese public hospitals is decided by the hospital Pharmacy Management Committee (PMC), that is complex, subjective and requires efficient approaches to ensure transparency and consistency for the factors being considered. This study aimed to use the Evidence and Value: Impact on Decision Making (EVIDEM) framework to assess medicine in these hospitals. In this study anti-diabetic drugs DPP-4 inhibitors, which work by inhibiting the activation of the Dipeptidyl Peptidase 4 (DPP-4) inhibitors, were appraised. METHODS: Following EVIDEM methodology (EVIDEM-10th), we convened an appraisal group and asked each individual to express their perspectives by assigning weights to each criterion. A systematic literature search for information of each criterion of five DPP-4 inhibitors was completed. Then the appraisal group scored for each criterion of the five DPP-4 inhibitors. The estimated value of the five DPP-4 inhibitors was obtained by Multi-Criteria Decision Analysis (MCDA) which combined individual weighting of each criterion with individual scoring for each intervention in each criterion. RESULTS: By assigning weights, the most important criterion was the quality of evidence (4.01±0.52), and that the comparative cost consequences-non-medical cost was the least important criterion (2.87±1.03). Criteria included disease severity, size of the affected population, comparative effectiveness, type of therapeutic/preventive benefit and cost of intervention, all of which were assigned the same weight of 3.58. After MCDA, the overall value orders for each DPP-4 inhibitor included Sitagliptin (0.45), Linagliptin (0.44), Vildagliptin (0.43), Alogliptin (0.42) and Saxagliptin (0.40). CONCLUSIONS: Based on EVIDEM framework and MCDA, we found that overall value of five DPP-4 inhibitors was similar. It is feasible to use the EVIDEM framework and MCDA in purchasing medicine for Chinese public hospitals.


Assuntos
Diabetes Mellitus Tipo 2 , Inibidores da Dipeptidil Peptidase IV , China , Tomada de Decisões , Técnicas de Apoio para a Decisão , Diabetes Mellitus Tipo 2/tratamento farmacológico , Dipeptidil Peptidase 4 , Hospitais Públicos , Humanos
11.
Intern Med ; 60(15): 2375-2383, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34334589

RESUMO

Objective Glucose-dependent insulinotropic polypeptide (GIP) is speculated to worsen growth hormone (GH) hypersecretion in acromegaly and to be a cause of paradoxical increases in GH (PI-GH) during 75-g oral glucose tolerance testing (75-g OGTT). Dipeptidyl peptidase-4 inhibitors (DPP4is), which increase the circulating concentration of active GIP, are frequently administered to diabetic patients, including those with acromegaly. We aimed to determine whether or not the administration of a DPP4i increases GH concentration, especially in patients demonstrating PI-GH during a DPP4i-OGTT, in which a DPP4i was administered immediately before 75-g OGTT. Methods This prospective cross-sectional study was carried out on acromegalic patients admitted to Hokkaido University hospital between June 2011 and May 2018. The participants underwent both 75-g OGTT and DPP4i-OGTT. For those who underwent surgery, immunohistochemical staining and quantitative polymerase chain reaction (PCR) for the GIP receptor (GIPR) were performed on the resected pituitary adenomas. Results Twenty-five percent of the participants had PI-GH confirmed (3 of 12 cases). Two of the three participants who demonstrated PI-GH exhibited higher circulating GH concentrations during DPP4i-OGTT than during OGTT. The increase in plasma glucose was reduced during DPP4i-OGTT compared to during 75-g OGTT, suggesting that the increase in GH during DPP4i-OGTT was due not to high glucose concentrations but instead increased GIP caused by the administration of DPP4i. The adenoma from one participant with PI-GH displayed positive immunostaining for GIPR and a higher GIPR messenger ribonucleic acid (mRNA) expression than the others. Conclusion DPP4i may enhance the GH secretion response during glucose loading, especially in individuals with PI-GH.


Assuntos
Acromegalia , Inibidores da Dipeptidil Peptidase IV , Hormônio do Crescimento Humano , Acromegalia/tratamento farmacológico , Estudos Transversais , Dipeptidil Peptidases e Tripeptidil Peptidases , Glucose , Hormônio do Crescimento , Humanos , Estudos Prospectivos
12.
J Fam Pract ; 70(6S): S1-S6, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34432617

RESUMO

LEARNING OBJECTIVES: At the end of the activity, participants will be able to: • Identify how heart failure (HF), chronic kidney disease (CKD), and type 2 diabetes mellitus (T2DM) and associated cardiovascular (CV) risks are interconnected. • Initiate guideline-recommended therapy to reduce CV risk in patients with HF, CKD, and/or T2DM. • Apply evidence for sodium-glucose cotransporter-2 inhibitors (SGLT-2 inhibitors) to clinical practice, based on recent and emerging trials. • Review evidence suggesting increased incidence and severity of COVID-19 infection in patients with diabetes.


Assuntos
Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/prevenção & controle , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Sistema Cardiovascular/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/prevenção & controle , Cardiomiopatias Diabéticas/tratamento farmacológico , Cardiomiopatias Diabéticas/prevenção & controle , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/prevenção & controle , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Humanos , Hipoglicemiantes/uso terapêutico , Resultado do Tratamento
13.
J Dermatol ; 48(10): 1584-1587, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34265108

RESUMO

Dipeptidyl peptidase 4 inhibitors (DPP-4i) are associated with an increased risk of developing bullous pemphigoid (BP) in patients with diabetes. Autoantibodies targeting epitopes on the processed BP180, 120-kDa (LAD-1), and 97-kDa (LABD97) linear immunoglobulin (Ig)A dermatosis antigens are the major autoantibodies in DPP-4i-associated BP. However, no case of mucous membrane pemphigoid (MMP) developing during treatment with DPP-4i has been reported. We report a case of MMP associated with DPP-4i. A man in his late 70s presented with oral mucous membrane erosion and a few blisters on his upper chest and back. He had used linagliptin for diabetes for over 1 year when he presented. The immunological characteristics were similar to DPP4i-associated BP: higher reactivity to LAD-1 and LABD97 than to the full-length BP180. The aphthae achieved remission after oral linagliptin was replaced with sitagliptin. However, 6 months later, the aphthae relapsed and any DPP-4i was discontinued. The aphthae disappeared, and now he is completely free from lesions associated with MMP. This case suggests that the DPP-4i may have shared roles in the production of IgG antibodies to LAD-1 or to LABD97 in the pathogenesis of DPP-4i-associated BP and MMP. Our case highlights the possibility of overlooking the mild MMP in DPP-4i-treated diabetes patients with mucosal lesions.


Assuntos
Diabetes Mellitus Tipo 2 , Inibidores da Dipeptidil Peptidase IV , Penfigoide Mucomembranoso Benigno , Penfigoide Bolhoso , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Humanos , Linagliptina/efeitos adversos , Masculino , Membrana Mucosa , Penfigoide Mucomembranoso Benigno/diagnóstico , Penfigoide Mucomembranoso Benigno/tratamento farmacológico , Penfigoide Bolhoso/induzido quimicamente , Penfigoide Bolhoso/tratamento farmacológico
15.
Int J Mol Sci ; 22(12)2021 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-34205264

RESUMO

Patients with type 2 diabetes have an increased risk of fracture compared to the general population. Glucose absorption is accelerated by incretin hormones, which induce insulin secretion from the pancreas. The level of the incretin hormone, glucagon-like peptide-1 (GLP-1), shows an immediate postprandial increase, and the circulating level of intact GLP-1 is reduced rapidly by dipeptidyl peptidase-4 (DPP-4)-mediated inactivation. Therefore, GLP-1 receptor agonists and DPP-4 inhibitors are effective in the treatment of type 2 diabetes. However, these incretin-related diabetic agents have been reported to affect bone metabolism, including bone formation and resorption. These agents enhance the expression of bone markers, and have been applied to improve bone quality and bone density. In addition, they have been reported to suppress chronic inflammation and reduce the levels of inflammatory cytokine expression. Previously, we reported that these incretin-related agents inhibited both the expression of inflammatory cytokines and inflammation-induced bone resorption. This review presents an overview of current knowledge regarding the effects of incretin-related diabetes drugs on osteoblast differentiation and bone formation as well as osteoclast differentiation and bone resorption. The mechanisms by which incretin-related diabetes drugs regulate bone formation and bone resorption are also discussed.


Assuntos
Reabsorção Óssea , Inibidores da Dipeptidil Peptidase IV/farmacologia , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Osteogênese/efeitos dos fármacos , Animais , Diabetes Mellitus/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Humanos
16.
J Proteome Res ; 20(8): 3798-3813, 2021 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-34254800

RESUMO

Picrorhiza kurroa Royle ex Benth. is a high-altitude plant having great medicinal value. However, its medicinal value at the peptide level is still unknown, which limits its utility in the development of peptide-based therapeutics. Here, we identify 65 peptides fromP. kurroa hydrolysate. Sequence analysis suggests that one novel bioactive peptide, ASGLCPEEAVPRR (BP1), has antioxidant potential and shows angiotensin-converting enzyme (ACE) and dipeptidyl peptidase-IV (DPP-IV) inhibitory activities. The molecular docking study showed that BP1 has a lower binding energy and strong affinity toward active pockets of ACE and DPP-IV, which explains its higher ACE [IC50 = 59.90 ± 9.52 µg/mL (43.40 µM)] and DPP-IV [IC50 = 3.04 ± 0.26 µg/mL (2.2 µM)] inhibitory activities. BP1 protects HEK293 cells from H2O2-induced oxidative damage by inhibiting intracellular reactive oxygen species (ROS) and malondialdehyde accumulation and activating the intrinsic antioxidant defense system. Additionally, phase-contrast microscopy studies revealed that pre-treatment of BP1 to HEK293 cells before exposure to H2O2 retains the normal morphology and blocks apoptosis. Furthermore, it also suppresses ROS-induced mitochondrial apoptosis via restoring the mitochondrial membrane potential (ΔΨm) and inhibiting caspase 3/7 activity. Therefore, BP1 has antioxidant potential and ACE and DPP-IV inhibitory activities that could be used for peptide-based formulation(s) in pharmaceuticals to treat diabetes, cardiovascular diseases, and other diseases associated with ROS.


Assuntos
Inibidores da Dipeptidil Peptidase IV , Picrorhiza , Células HEK293 , Humanos , Peróxido de Hidrogênio , Simulação de Acoplamento Molecular , Estresse Oxidativo , Peptídeos/metabolismo , Picrorhiza/metabolismo
17.
Endocrinol Metab (Seoul) ; 36(4): 904-908, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34311543

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic remains an unbeaten enemy. Unfortunately, no targeted treatment option is available. Patients with type 2 diabetes mellitus (T2DM) have increased odds for severe or fatal disease, as demonstrated in recent observational studies. There is an ongoing discussion regarding the impact of different antidiabetic drug classes on outcomes of interest among affected subjects. Dipeptidyl peptidase-4 (DPP-4) inhibitors have been placed at the epicenter, since the DPP-4 enzyme seems to be implicated in the disease pathogenesis. Herein we present an updated meta-analysis of observational studies addressing the risk of COVID-19 death among patients with T2DM on prior DPP-4 inhibitor treatment. We pooled data from 10 observational studies, showing that DPP-4 inhibitors produce a non-significant decrease in the risk for COVID-19-related death. However, when administered in the inpatient setting, DPP-4 inhibitors decrease the risk for COVID-19-related death by 50%. Ongoing randomized controlled trials will shed further light.


Assuntos
COVID-19/tratamento farmacológico , COVID-19/mortalidade , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/mortalidade , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Estudos Observacionais como Assunto/métodos , COVID-19/sangue , Diabetes Mellitus Tipo 2/sangue , Dipeptidil Peptidase 4/sangue , Inibidores da Dipeptidil Peptidase IV/farmacologia , Humanos , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Mortalidade/tendências
18.
S D Med ; 74(3): 132-135, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34232594

RESUMO

Diabetes mellitus remains one of the most common and disabling diseases in the world. Patients with diabetes tend to have more cardiovascular complications, regardless of their prior cardiac history. Tight glycemic control has been shown to prevent microvascular complications as it relates to nephropathy and retinopathy; however, it hasn't been proven beneficial in patients with macrovascular diseases, i.e., cardiovascular disease. In fact, two groups of diabetic medications, dual peroxisome-proliferator-activated receptor - agonists and sulfonylurea, are known to worsen cardiovascular disease. Patients using this group of medications have shown increased heart failure readmission rates and increased risk for cardiovascular death. Insulin and Metformin have been the gold standard treatment for diabetes management to prevent worsening cardiac outcomes, and now a newer class of medications have demonstrated similar results. These drug classes includes sodium glucose cotransporter 2(SGLT 2) inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, and glucagon like peptide-1 (GLP 1) analogues.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Inibidores da Dipeptidil Peptidase IV , Inibidores do Transportador 2 de Sódio-Glicose , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Peptídeo 1 Semelhante ao Glucagon , Humanos , Hipoglicemiantes/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico
19.
Int J Mol Sci ; 22(14)2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34299225

RESUMO

COVID-19 infection poses an important clinical therapeutic problem, especially in patients with coexistent diseases such as type 2 diabetes. Potential pathogenetic links between COVID-19 and diabetes include inflammation, effects on glucose homeostasis, haemoglobin deoxygenation, altered immune status and activation of the renin-angiotensin-aldosterone system (RAAS). Moreover, drugs often used in the clinical care of diabetes (dipeptidyl peptidase 4 inhibitors, glucagon-like peptide 1 receptor agonists, sodium-glucose cotransporter 2 inhibitors, metformin and insulin) may influence the course of SARS-CoV-2 infection, so it is very important to verify their effectiveness and safety. This review summarises the new advances in diabetes therapy and COVID-19 and provides clinical recommendations that are essential for medical doctors and for patients suffering from type 2 diabetes.


Assuntos
COVID-19/terapia , Diabetes Mellitus Tipo 2/terapia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , COVID-19/complicações , COVID-19/epidemiologia , COVID-19/fisiopatologia , Diabetes Mellitus Tipo 2/fisiopatologia , Diabetes Mellitus Tipo 2/virologia , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Humanos , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Metformina/uso terapêutico , SARS-CoV-2/isolamento & purificação , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico
20.
Diab Vasc Dis Res ; 18(3): 14791641211021585, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34182806

RESUMO

BACKGROUND: Type 2 diabetes (T2D) is associated with an increased risk of cardiovascular (CV) disease. In patients with T2D and established CV disease, selective inhibitors of sodium-glucose cotransporter 2 (SGLT2) have been shown to decrease CV and all-cause mortality, and heart failure (HF) admissions. Utilising CV magnetic resonance imaging (CMR) and continuous glucose monitoring (CGM) by FreeStyle Libre Pro Sensor, we aim to explore the mechanisms of action which give Empagliflozin, an SGLT2 inhibitor, its beneficial CV effects and compare these to the effects of dipeptidyl peptidase-4 inhibitor Sitagliptin. METHODS: This is a single centre, open-label, cross-over trial conducted at the Leeds Teaching Hospitals NHS Trust. Participants are randomised for the order of treatment and receive 3 months therapy with Empagliflozin, and 3 months therapy with Sitagliptin sequentially. Twenty-eight eligible T2D patients with established ischaemic heart disease will be recruited. Patients undergo serial CMR scans on three visits. DISCUSSION: The primary outcome measure is the myocardial perfusion reserve in remote myocardium. We hypothesise that Empaglifozin treatment is associated with improvements in myocardial blood flow and reductions in myocardial interstitial fibrosis, independent of CGM measured glycemic control in patients with T2D and established CV disease. TRIAL REGISTRATION: This study has full research ethics committee approval (REC: 18/YH/0190) and data collection is anticipated to finish in December 2021. This study was retrospectively registered at https://doi.org/10.1186/ISRCTN82391603 and monitored by the University of Leeds. The study results will be submitted for publication within 6 months of completion.


Assuntos
Compostos Benzidrílicos/uso terapêutico , Circulação Coronária/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Glucosídeos/uso terapêutico , Controle Glicêmico , Isquemia Miocárdica/tratamento farmacológico , Fosfato de Sitagliptina/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Compostos Benzidrílicos/efeitos adversos , Estudos Cross-Over , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Inglaterra , Fibrose , Glucosídeos/efeitos adversos , Controle Glicêmico/efeitos adversos , Humanos , Isquemia Miocárdica/diagnóstico por imagem , Isquemia Miocárdica/fisiopatologia , Miocárdio/patologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Fosfato de Sitagliptina/efeitos adversos , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
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