scholarly journals Dipeptidyl Peptidase 4: A New Link between Diabetes Mellitus and Atherosclerosis?

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Wellington Santana da Silva Júnior ◽  
Amélio Fernando de Godoy-Matos ◽  
Luiz Guilherme Kraemer-Aguiar
Keyword(s):  
Diabetes Mellitus ◽  
Vascular Function ◽  
Dipeptidyl Peptidase ◽  
Noncommunicable Diseases ◽  
Atherosclerotic Cardiovascular Disease ◽  
Dipeptidyl Peptidase 4 ◽  
Increased Risk ◽  
Increase Insulin Secretion

Type 2 diabetes mellitus (T2DM) has become one of the most prevalent noncommunicable diseases in the past years. It is undoubtedly associated with atherosclerosis and increased risk for cardiovascular diseases. Incretins, which are intestinal peptides secreted during digestion, are able to increase insulin secretion and its impaired function and/or secretion is involved in the pathophysiology of T2DM. Dipeptidyl peptidase 4 (DPP4) is an ubiquitous enzyme that regulates incretins and consequently is related to the pathophysiology of T2DM. DPP4 is mainly secreted by endothelial cells and acts as a regulatory protease for cytokines, chemokines, and neuropeptides involved in inflammation, immunity, and vascular function. In T2DM, the activity of DPP4 seems to be increased and there are a growing number ofin vitroandin vivostudies suggesting that this enzyme could be a new link between T2DM and atherosclerosis. Gliptins are a new class of pharmaceutical agents that acts by inhibiting DPP4. Thus, it is expected that gliptin represents a new pharmacological approach not only for reducing glycemic levels in T2DM, but also for the prevention and treatment of atherosclerotic cardiovascular disease in diabetic subjects. We aimed to review the evidences that reinforce the associations between DPP4, atherosclerosis, and T2DM.

scholarly journals Dipeptidyl peptidase-4 inhibitor protects against non-alcoholic steatohepatitis in mice by targeting TRAIL receptor-mediated lipoapoptosis via modulating hepatic dipeptidyl peptidase-4 expression

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Minyoung Lee ◽  
Eugene Shin ◽  
Jaehyun Bae ◽  
Yongin Cho ◽  
Ji-Yeon Lee ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Dipeptidyl Peptidase ◽  
Trail Receptor ◽  
Dipeptidyl Peptidase 4 ◽  
Alcoholic Steatohepatitis ◽  
Dipeptidyl Peptidase 4 Inhibitors ◽  
Group 2 ◽  
Induced Apoptosis

Abstract Dipeptidyl peptidase-4 inhibitors (DPP4i) are antidiabetic medications that prevent cleavage of incretin hormones by dipeptidyl peptidase-4 (DPP4). DPP4 is ubiquitously expressed, and its hepatic DPP4 expression is upregulated under non-alcoholic steatohepatitis (NASH) conditions. We investigated the effect of DPP4i treatment on NASH pathogenesis, as well as its potential underlying molecular mechanisms. Mice were randomly divided into three groups: Group 1, chow-fed mice treated with vehicle for 20 weeks; Group 2, high-fat, high-fructose, and high-cholesterol Amylin liver NASH (AMLN) diet-fed mice treated with vehicle for 20 weeks; Group 3, AMLN diet-fed mice treated with vehicle for the first 10 weeks, followed by the DPP4i teneligliptin (20 mg/kg/day) for additional 10 weeks. DPP4i administration reduced serum liver enzyme and hepatic triglyceride levels and markedly improved hepatic steatosis and fibrosis in the AMLN diet-induced NASH model. In vivo, NASH alleviation significantly correlated with the suppression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor-mediated apoptosis and downregulated hepatic DPP4 expression. In vitro, DPP4i treatment significantly decreased the markers of TRAIL receptor-mediated lipoapoptosis and suppressed DPP4 expression in palmitate-treated hepatocytes. In conclusion, DPP4i may efficiently attenuate the pathogenesis of AMLN diet-induced NASH in mice by suppressing lipotoxicity-induced apoptosis, possibly by modulating hepatic DPP4 expression.

scholarly journals Adipose Dipeptidyl Peptidase-4 and Obesity: Correlation with insulin resistance and depot-specific release from adipose tissue in vivo and in vitro

Diabetes Care ◽  
2013 ◽  
Vol 36 (12) ◽  
pp. 4083-4090 ◽  
Author(s):  
H. Sell ◽  
M. Bluher ◽  
N. Kloting ◽  
R. Schlich ◽  
M. Willems ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase 4

Glucagon-like peptide-1 response to whey protein is less diminished by dipeptidyl peptidase-4 in comparison with responses to dextrin, a lipid and casein in rats

2020 ◽  
pp. 1-10 ◽  
Author(s):  
Yuki Shimizu ◽  
Hiroshi Hara ◽  
Tohru Hira
Keyword(s):  
Whey Protein ◽  
Dipeptidyl Peptidase ◽  
Dietary Proteins ◽  
Sprague Dawley ◽  
Dipeptidyl Peptidase 4 ◽  
Sprague Dawley Rats ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Abstract Although glucose is the best-known nutrient to stimulate glucagon-like peptide-1 (GLP-1) secretion, dietary peptides also potently stimulate GLP-1 secretion. Certain peptide fragments derived from dietary proteins possess dipeptidyl peptidase-4 (DPP-4) inhibitory activity in vitro. Hence, we hypothesised that dietary peptides protect GLP-1 from degradation through attenuating DPP-4 activity in vivo. Here, we compared GLP-1 responses with dietary proteins, a carbohydrate and a lipid (Intralipos) in rats having or not having plasma DPP-4 activity. Plasma GLP-1 concentrations clearly increased by oral administration of whey protein (2–4 g/kg), but not by that of dextrin (2–4 g/kg), in control rats (untreated Sprague–Dawley rats and F344/Jcl rats), having DPP-4 activity. In contrast, dextrin administration increased the plasma GLP-1 concentrations as the whey protein administration did, in rats having reduced or no DPP-4 activity (a DPP-4 inhibitor, sitagliptin-treated Sprague–Dawley rats or DPP-4-deficient F344/DuCrl/Crlj rats). DPP-4 inhibition by sitagliptin treatment also enhanced GLP-1 response to Intralipos, and casein, but the treatment did not further enhance GLP-1 response to whey protein. Intestinal GLP-1 content and gastric emptying rate were not associated with differences in GLP-1 responses to test nutrients. The luminal contents from rats administered whey protein decreased DPP-4 activity in vitro. These results suggest that GLP-1 released by dextrin, Intralipos and casein was immediately degraded by DPP-4, while GLP-1 released by whey protein was less degraded. Our study provides novel in vivo evidence supporting the hypothesis that dietary peptides not only stimulate GLP-1 secretion but also inhibit DPP-4 activity to potentiate GLP-1 response.

scholarly journals Polyalthia Clerodane Diterpene Potentiates Hypoglycemia via Inhibition of Dipeptidyl Peptidase 4

2019 ◽  
Vol 20 (3) ◽  
pp. 530 ◽  
Author(s):  
Po-Kai Huang ◽  
Shian-Ren Lin ◽  
Jirawat Riyaphan ◽  
Yaw-Syan Fu ◽  
Ching-Feng Weng
Keyword(s):  
Single Dose ◽  
Natural Compounds ◽  
Dipeptidyl Peptidase ◽  
Antidiabetic Activity ◽  
Drug Candidate ◽  
Diabetic Patients ◽  
Dose Administration ◽  
Dipeptidyl Peptidase 4

Serine protease dipeptidyl peptidase 4 (DPP-4) is involved in self/non-self-recognition and insulin sensitivity. DPP-4 inhibitors are conventional choices for diabetic treatment; however, side effects such as headache, bronchus infection, and nasopharyngitis might affect the daily lives of diabetic patients. Notably, natural compounds are believed to have a similar efficacy with lower adverse effects. This study aimed to validate the DPP-4 inhibitory activity of clerodane diterpene 16-hydroxycleroda-3,13-dien-15,16-olide (HCD) from Polyalthia longifolia, rutin, quercetin, and berberine, previously selected through molecular docking. The inhibitory potency of natural DPP-4 candidates was further determined by enzymatic, in vitro Caco-2, and ERK/PKA activation in myocyte and pancreatic cells. The hypoglycemic efficacy of the natural compounds was consecutively analyzed by single-dose and multiple-dose administration in diet-induced obese diabetic mice. All the natural-compounds could directly inhibit DPP-4 activity in enzymatic assay and Caco-2 inhibition assay, and HCD showed the highest inhibition of the compounds. HCD down-regulated LPS-induced ERK phosphorylation in myocyte but blocked GLP-1 induced PKA expression. For in vivo tests, HCD showed hypoglycemic efficacy only in single-dose administration. After 28-days administration, HCD exhibited hypolipidemic and hepatoprotective efficacy. These results revealed that HCD performed potential antidiabetic activity via inhibition of single-dose and long-term administrations, and could be a new prospective anti-diabetic drug candidate.

scholarly journals The persistent inhibitory properties of saxagliptin on renal dipeptidyl peptidase-4: Studies with HK-2 cells in vitro and normal rats in vivo

2017 ◽  
Vol 135 (3) ◽  
pp. 126-130 ◽  
Author(s):  
Masako Uchii ◽  
Mariko Sakai ◽  
Yuhei Hotta ◽  
Satoshi Saeki ◽  
Naoya Kimoto ◽  
...  
Keyword(s):  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase 4

Platelets, vascular disease, and diabetes mellitus

1994 ◽  
Vol 72 (3) ◽  
pp. 295-303 ◽  
Author(s):  
Peter D. Winocour
Keyword(s):  
Diabetes Mellitus ◽  
Vascular Disease ◽  
Platelet Activity ◽  
Platelet Surface ◽  
Clinical Complications ◽  
Fibrinogen Binding ◽  
Increased Risk ◽  
Adhesive Proteins

Diabetes is associated with increased risk for atherosclerosis and its thromboembolic complications. Theories about mechanisms of atherosclerosis in diabetes are similar to those in the nondiabetic population. Platelets contribute to atherosclerosis through effects on vessels by materials released from the platelets, which interact with injured or altered vessels. In diabetes, platelets could contribute to enhanced atherosclerosis through hypersensitivity to agonists at sites of vessel injury and increased release of materials from adherent platelets. Diabetic platelets are hypersensitive to agonists in vitro, and alterations in a number of mechanisms involved in platelet activation occur in these platelets, which could contribute to the hypersensitivity. These alterations include increased presence of glycoprotein receptors for agonists and adhesive proteins on the platelet surface, increased fibrinogen binding, decreased membrane fluidity, enhanced arachidonate pathway activation with increased thromboxane A2 formation, and increased phosphoinositide turnover leading to increased inositol trisphosphate production, Ca2+ mobilization, and protein phosphorylation. There is some evidence for increased platelet activity in vivo in diabetes, but it is unclear whether this reflects platelet hypersensitivity or increased platelet turnover on already diseased vessels. Studies in diabetic animals indicate greater interaction of platelets with injured vessels and incorporation into experimentally induced thrombi, but it is unclear if this reflects changes in platelets or other factors. These changes could be contributing to the enhanced atherosclerosis and its clinical complications in diabetic patients.Key words: platelets, vascular disease, diabetes mellitus.

scholarly journals Antioxidant Activity of Pigmented Rice and Impact on Health

JURNAL PANGAN ◽  
2019 ◽  
Vol 28 (1) ◽  
pp. 11-22
Author(s):  
Arfina Sukmawati Arifin
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Antioxidant Activity ◽  
Vascular Function ◽  
Healthy Lifestyle ◽  
Cell Damage ◽  
The Body ◽  
Food Sources

The high number of free radicals that are not balanced with the amount of antioxidants in the body triggers oxidative stress. Oxidative stress causes impaired vascular function, damage to proteins and lipids in membrane cell, and nucleic acid (DNA) mutations. Chronic cell damage has a negative effect on tissue that triggers various diseases such as neurodegenerative diseases (Alzheimer's, Parkinson's), cardiovascular diseases (hypertension, arteriosclerosis, and others), cataracts, retinal damage, maculopathy, rheumatoid arthritis, asthma, stroke, diabetes mellitus , immunodepression, cancer, aging, hyperoxia, dermatitis, and others. The application of a healthy lifestyle for example by consuming food sources of bioactive compounds can minimize health risks. Rice is the staple food of the Indonesian people. Some types of rice contain red and black pigments which are known to have high antioxidant activity compared to white rice. The pigment comes from anthocyanin and proanthocyanidin. Various studies in vitro and in vivo prove that anthocyanin and proantocyanidine act as antioxidants and potency as a preventative for various diseases such as cardiovascular, diabetes mellitus, and etc.

scholarly journals The Nonglycemic Actions of Dipeptidyl Peptidase-4 Inhibitors

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Na-Hyung Kim ◽  
Taeyang Yu ◽  
Dae Ho Lee
Keyword(s):  
Randomized Clinical Trials ◽  
Cardiovascular Effects ◽  
Dipeptidyl Peptidase ◽  
Protective Effects ◽  
Dipeptidyl Peptidase 4 ◽  
Dipeptidyl Peptidase 4 Inhibitors ◽  
Glucagon Like Peptide 1 ◽  
Stimulation Of

A cell surface serine protease, dipeptidyl peptidase 4 (DPP-4), cleaves dipeptide from peptides containing proline or alanine in the N-terminal penultimate position. Two important incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP), enhance meal-stimulated insulin secretion from pancreaticβ-cells, but are inactivated by DPP-4. Diabetes and hyperglycemia increase the DPP-4 protein level and enzymatic activity in blood and tissues. In addition, multiple other functions of DPP-4 suggest that DPP-4 inhibitor, a new class of antidiabetic agents, may have pleiotropic effects. Studies have shown that DPP-4 itself is involved in the inflammatory signaling pathway, the stimulation of vascular smooth cell proliferation, and the stimulation of oxidative stress in various cells. DPP-4 inhibitor ameliorates these pathophysiologic processes and has been shown to have cardiovascular protective effects in bothin vitroandin vivoexperiments. However, in recent randomized clinical trials, DPP-4 inhibitor therapy in high risk patients with type 2 diabetes did not show cardiovascular protective effects. Some concerns on the actions of DPP-4 inhibitor include sympathetic activation and neuropeptide Y-mediated vascular responses. Further studies are required to fully characterize the cardiovascular effects of DPP-4 inhibitor.

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