RESUMO
Dipeptidyl peptidase IV (DPP-IV) inhibitory peptides were screened and identified from yak hemoglobin for the first time by in silico analysis, molecular docking, and in vitro evaluation. Results showed that yak hemoglobin had a high potential to produce DPP-IV inhibitory peptides based on the sequence alignment and bioactive potential evaluation. Furthermore, "pancreatic elastase + stem bromelain" was the optimal combined-enzymatic strategy by simulated proteolysis. Additionally, 25 novel peptides were found from its simulated hydrolysate, among which 10 peptides had high binding affinities with DPP-IV by molecular docking. Most of these peptides were also in silico characterized with favorable physicochemical properties and biological potentials, including relatively low molecular weight, high hydrophobicity, several net charges, good water solubility, nontoxicity, acceptable sensory quality, and good human intestinal absorption. Finally, six novel DPP-IV inhibitory peptides were identified via in vitro assessment, among which EEKA (IC50 = 235.26 µM), DEV (IC50 = 339.45 µM), and HCDKL (IC50 = 632.93 µM) showed the strongest capacities. The hydrogen bonds and electrostatic attractions formed with core residues within the S2 pocket of DPP-IV could be mainly responsible for their inhibition performances. This work provided a time-saving method and broadened application for yak by-products development as sources of functional foods.
Assuntos
Dipeptidil Peptidase 4 , Inibidores da Dipeptidil Peptidase IV , Animais , Bovinos , Humanos , Simulação de Acoplamento Molecular , Dipeptidil Peptidase 4/química , Inibidores da Dipeptidil Peptidase IV/farmacologia , Inibidores da Dipeptidil Peptidase IV/química , Peptídeos/química , HemoglobinasRESUMO
Highlights Based on nationwide insurance data in Korea, the use of dipeptidyl peptidase IV inhibitors (DPP-IVi) not requiring renal dose adjustment (NRDA DPP-IVi) is widespread in the type 2 diabetes chronic kidney disease (T2D CKD) population. Instead of prescribing NRDA DPP-IVi, the use of DPP-IVi requiring renal dose adjustment with appropriate renal dose adjustments in T2D CKD patients can achieve a considerable annual cost saving of up to 7.8%.
Assuntos
Análise Custo-Benefício , Diabetes Mellitus Tipo 2/tratamento farmacológico , Nefropatias Diabéticas/economia , Inibidores da Dipeptidil Peptidase IV/economia , Custos de Cuidados de Saúde , Insuficiência Renal Crônica/economia , Adulto , Biomarcadores/análise , Glicemia/análise , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/economia , Diabetes Mellitus Tipo 2/patologia , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/etiologia , Dipeptidil Peptidase 4/química , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Relação Dose-Resposta a Droga , Cálculos da Dosagem de Medicamento , Feminino , Seguimentos , Hemoglobinas Glicadas/análise , Humanos , Masculino , Prognóstico , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/etiologia , Adulto JovemRESUMO
LTFPGSAED (P7) is a multifunctional hypocholesterolemic and hypoglycemic lupin peptide. While assessing its angiotensin-converting enzyme (ACE) inhibitory activity, it was more effective in intestinal Caco-2 cells (IC50 of 13.7 µM) than in renal HK-2 cells (IC50 of 79.6 µM). This discrepancy was explained by the metabolic transformation mediated by intestinal peptidases, which produced two main detected peptides, TFPGSAED and LTFPG. Indeed LTFPG, dynamically generated by intestinal dipeptidyl peptidase IV as well as its parent peptide P7 were linearly absorbed by mature Caco-2 cells. An in silico study demonstrated that the metabolite was a better ligand of the ACE enzyme than P7. These results are in agreement with an in vivo study, previously performed by Aluko et al., which has shown that LTFPG is an effective hypotensive peptide. Our work highlights the dynamic nature of bioactive food peptides that may be modulated by the metabolic activity of intestinal cells.
Assuntos
Inibidores da Dipeptidil Peptidase IV/química , Lupinus/química , Peptídeos/química , Transporte Biológico , Células CACO-2 , Dipeptidil Peptidase 4/química , Dipeptidil Peptidase 4/metabolismo , Inibidores da Dipeptidil Peptidase IV/metabolismo , Humanos , Espectrometria de Massas , Simulação de Acoplamento Molecular , Peptídeos/metabolismo , Extratos Vegetais/química , Extratos Vegetais/metabolismoRESUMO
In this study, the potential bioactivities of Portuguese oyster (Crassostrea angulata) proteins were predicted through in silico analyses and confirmed by in vitro tests. C. angulata proteins were characterized by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and identified by proteomics techniques. Hydrolysis simulation by BIOPEP-UWM database revealed that pepsin (pH > 2) can theoretically release greatest amount of bioactive peptides from C. angulata proteins, predominantly angiotensin I-converting enzyme (ACE) and dipeptidyl peptidase IV (DPP-IV) inhibitory peptides, followed by stem bromelain and papain. Hydrolysates produced by pepsin, bromelain and papain have shown ACE and DPP-IV inhibitory activities in vitro, with pepsin hydrolysate (PEH) having the strongest activity of 78.18% and 44.34% at 2 mg/mL, respectively. Bioactivity assays of PEH fractions showed that low molecular weight (MW) fractions possessed stronger inhibitory activity than crude hydrolysate. Overall, in vitro analysis results corresponded with in silico predictions. Current findings suggest that in silico analysis is a rapid method to predict bioactive peptides in food proteins and determine suitable enzymes for hydrolysis. Moreover, C. angulata proteins can be a potential source of peptides with pharmaceutical and nutraceutical application.
Assuntos
Inibidores da Enzima Conversora de Angiotensina/farmacologia , Crassostrea/metabolismo , Inibidores da Dipeptidil Peptidase IV/farmacologia , Fragmentos de Peptídeos/farmacologia , Hidrolisados de Proteína/metabolismo , Proteoma/análise , Animais , Simulação por Computador , Dipeptidil Peptidase 4/química , Técnicas In Vitro , Peptidil Dipeptidase A/químicaRESUMO
Prediabetes increases an individual's risk for progress to diabetes. The aim of the study is to assess prediabetic profile before and after life style modification only, lifestyle with metformin and lifestyle with DPP-4 inhibitor. This study was carried out at BIRDEM. The subjects were IGT, IFG or combined. In Group A 50 subjects were advised with lifestyle, 42 were follow up with the results showed that highly significant change in BMI, Fasting & 2â¯h plasma glucose, serum triglyceride, and reduced HbA1c level, reduction rate of DM is 43%. In Group B 50 subjects were advised with lifestyle plus metformin, 44 were follow up with the results showed that significant change in BMI, Fasting, 2â¯h plasma glucose, triglyceride, and reduced HbA1c, reduction rate of DM is 58%. In Group C 50 subjects were advised with lifestyle plus DPP4i, 37 were follow up with the results showed that significantly change in BMI, Fasting, 2â¯h plasma glucose, triglyceride and reduced HbA1c level, reduction rate of DM is 43%. There is significant outcome difference in BMI in between A vs. B and A vs. C group. More mean changed in 2hrs after blood glucose level in group A vs. group B and B vs. C group. There is significant outcome difference in TG level in A vs. B, B vs. C group but no difference in A vs. C group.
Assuntos
Diabetes Mellitus Tipo 2/prevenção & controle , Dipeptidil Peptidase 4/química , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Hipoglicemiantes/uso terapêutico , Estilo de Vida , Metformina/uso terapêutico , Estado Pré-Diabético/terapia , Adulto , Bangladesh , Biomarcadores/análise , Glicemia/análise , Índice de Massa Corporal , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Feminino , Seguimentos , Hemoglobinas Glicadas/análise , Humanos , Masculino , Pessoa de Meia-Idade , Estado Pré-Diabético/metabolismo , Estado Pré-Diabético/patologia , PrognósticoRESUMO
In our previous study, Atlantic salmon skin gelatin hydrolysed with flavourzyme possessed 42.5% dipeptidyl-peptidase (DPP)-IV inhibitory activity at a concentration of 5 mg mL(-1). The oral administration of the hydrolysate (FSGH) at a single dose of 300 mg per day in streptozotocin (STZ)-induced diabetic rats for 5 weeks was evaluated for its antidiabetic effect. During the 5-week experiment, body weight increased, and the food and water intake was reduced by FSGH in diabetic rats. The daily administration of FSGH for 5 weeks was effective for lowering the blood glucose levels of diabetic rats during an oral glucose tolerance test (OGTT). After the 5-week treatment, plasma DPP-IV activity was inhibited; the plasma activity of glucagon-like peptide-1 (GLP-1), insulin, and the insulin-to-glucagon ratio were increased by FSGH in diabetic rats. The results indicate that FSGH has the function of inhibiting GLP-1 degradation by DPP-IV, resulting in the enhancement of insulin secretion and improvement of glycemic control in STZ-induced diabetic rats.
Assuntos
Diabetes Mellitus Tipo 2/dietoterapia , Suplementos Nutricionais , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Proteínas de Peixes/uso terapêutico , Gelatina/uso terapêutico , Hidrolisados de Proteína/uso terapêutico , Salmo salar , Animais , Colúmbia Britânica , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/metabolismo , Suplementos Nutricionais/economia , Dipeptidil Peptidase 4/sangue , Dipeptidil Peptidase 4/química , Dipeptidil Peptidase 4/metabolismo , Inibidores da Dipeptidil Peptidase IV/economia , Inibidores da Dipeptidil Peptidase IV/isolamento & purificação , Inibidores da Dipeptidil Peptidase IV/metabolismo , Endopeptidases/metabolismo , Proteínas de Peixes/economia , Proteínas de Peixes/isolamento & purificação , Proteínas de Peixes/metabolismo , Indústria de Processamento de Alimentos/economia , Gelatina/economia , Gelatina/isolamento & purificação , Gelatina/metabolismo , Glucagon/antagonistas & inibidores , Glucagon/sangue , Glucagon/metabolismo , Peptídeo 1 Semelhante ao Glucagon/agonistas , Peptídeo 1 Semelhante ao Glucagon/sangue , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Hiperglicemia/prevenção & controle , Resíduos Industriais/análise , Resíduos Industriais/economia , Insulina/agonistas , Insulina/sangue , Insulina/metabolismo , Secreção de Insulina , Masculino , Hidrolisados de Proteína/economia , Hidrolisados de Proteína/isolamento & purificação , Hidrolisados de Proteína/metabolismo , Ratos Sprague-Dawley , Pele/químicaRESUMO
The understanding of biological ligand-receptor binding processes is relevant for a variety of research topics and assists the rational design of novel drug molecules. Computer simulation can help to advance this understanding, but, due to the high dimensionality of according systems, suffers from the severe computational cost. Based on the framework provided by conformation dynamics and transition state theory, a novel heuristic approach of simulating ligand-receptor binding processes is introduced, which is not dependent on calculating lengthy molecular dynamics trajectories. First, the relevant portion of conformational space is partitioned with meshless methods. Then, each region is sampled separately, using hybrid Monte Carlo. Finally, the dynamical binding process is reconstructed from the static overlaps between the partial densities obtained in the sampling step. The method characterizes the metastable steps of the binding process and can yield the corresponding transition probabilities.