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dipeptidyl peptidase 4

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https://www.readbyqxmd.com/read/29150631/effect-of-long-term-incretin-based-therapies-on-ischemic-heart-diseases-in-patients-with-type-2-diabetes-mellitus-a-network-meta-analysis
#1
Che-Yi Chou, Ying-Tzu Chang, Jia-Lian Yang, Jiun-Yi Wang, Tsui-Er Lee, Ruey-Yun Wang, Chin-Chuan Hung
Patients with type 2 diabetes mellitus (T2DM) experience many cardiovascular complications. Several studies have demonstrated the cardioprotective effects of incretin-based therapies; however, there are few studies on the effects of long-term incretin-based therapies on cardiovascular events. Therefore, the present study conducted a systematic review and network meta-analysis to evaluate the effects of long-term incretin-based therapies on ischaemic diseases. We searched PubMed, CENTRAL, and Clinicaltrial.gov to retrieve randomised control trials reported until December 2016 and enrolled only RCTs with more than a 1-year follow-up...
November 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29149484/comparative-analysis-of-proteomes-between-diabetic-and-normal-human-sperm-insights-into-the-effects-of-diabetes-on-male-reproduction-based-on-the-regulation-of-mitochondria-related-proteins
#2
Tian An, Yue-Fen Wang, Jia-Xian Liu, Yan-Yun Pan, Yu-Fei Liu, Zhong-Chen He, Fang-Fang Mo, Jun Li, Li-Hua Kang, Yu-Jie Gu, Bo-Han Lv, Si-Huan Gao, Guang-Jian Jiang
This study sought to identify sources of the reduced fertility of men with type 2 diabetes mellitus. Significant reductions in semen volume, sperm concentration, and total sperm count were observed in diabetic individuals, while transmission electron microscopy revealed that the structure of mitochondria in the tail of sperm from diabetic patients was damaged. Proteins potentially associated with these sperm defects were identified using proteomics. Isobaric tagging for relative and absolute quantitation labeling and high-performance liquid chromatography-tandem mass spectrometry allowed us to identify 357 proteins significantly differentially expressed in diabetic versus control semen (>1...
November 17, 2017: Molecular Reproduction and Development
https://www.readbyqxmd.com/read/29148282/macrocarpal-c-isolated-from-eucalyptus-globulus-inhibits-dipeptidyl-peptidase-4-in-an-aggregated-form
#3
Eisuke Kato, Kazuhiro Kawakami, Jun Kawabata
Dipeptidyl peptidase 4 (DPP-4) inhibitors are used for the treatment of type-2 diabetes mellitus. Various synthetic inhibitors have been developed to date, and plants containing natural DPP-4 inhibitors have also been identified. Here, 13 plant samples were tested for their DPP-4 inhibitory activity. Macrocarpals A-C were isolated from Eucalyptus globulus through activity-guided fractionation and shown to be DPP-4 inhibitors. Of these, macrocarpal C showed the highest inhibitory activity, demonstrating an inhibition curve characterised by a pronounced increase in activity within a narrow concentration range...
December 2018: Journal of Enzyme Inhibition and Medicinal Chemistry
https://www.readbyqxmd.com/read/29146035/renal-outcomes-with-dipeptidyl-peptidase-4-inhibitors
#4
REVIEW
A J Scheen, P Delanaye
Dipeptidyl peptidase-4 inhibitors (DPP-4is) are increasingly being used in the management of type 2 diabetes (T2D). The present review summarizes the current knowledge of the effects of DPP-4is on renal outcomes by analyzing the experimental preclinical data, the effects of DPP-4is on urinary albumin-creatinine ratios (UACRs) and estimated glomerular filtration rates (eGFRs) from observational studies and clinical trials, and renal events (including kidney failure requiring renal replacement therapy) in recent large prospective cardiovascular outcome trials...
November 13, 2017: Diabetes & Metabolism
https://www.readbyqxmd.com/read/29145151/vildagliptin-loaded-triangular-dna-nanospheres-coated-with-eudragit-for-oral-delivery-and-better-glycemic-control-in-type-2-diabetes-mellitus
#5
Mirza Muhammad Faran Ashraf Baig, Sara Khan, Muhammad Ahsan Naeem, Ghulam Jilany Khan, Muhammad Tayyab Ansari
Diabetes mellitus type 2 is a multidimensional disease associated with poor glycemic control through compromised sensitivity of pancreatic islet α and β cells against glucose and dwindled secretion of insulin which is linked with the quantity of incretin hormones that are abridged by dipeptidyl peptidase-4 (DPP-4) in diseased condition. Vildagliptin (VG) inhibits DPP-4 therefore regulates the incretins that conversely maintains glycemic control. The safe reach and absorption of VG from intestine was dubious...
November 13, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29144805/dpp4-inhibitor-sitagliptin-as-a-potential-treatment-option-in-metformin-intolerant-obese-women-with-polycystic-ovary-syndrome-a-pilot-randomized-study
#6
Simona Ferjan, Andrej Janez, Mojca Jensterle
OBJECTIVE: Metformin has an established role in the management of polycystic ovary syndrome (PCOS). Some patients cannot tolerate it due to associated gastrointestinal adverse events. The present study evaluated DPP4 inhibitor sitagliptin as a potential treatment option in metformin intolerant PCOS. DESIGN: We conducted a 12-week prospective randomized open-label study with 30 obese metformin intolerant women with PCOS (aged 35.0±7.2 years, BMI 36.9±5.5 kg/m(2))...
November 16, 2017: Endocrine Practice
https://www.readbyqxmd.com/read/29142025/cardioprotection-of-dapagliflozin-and-vildagliptin-in-cardiac-reperfusion-injury-rats
#7
Pongpan Tanajak, Piangkwan Sa-Nguanmoo, Sivaporn Sivasinprasan, Savitree Thummasorn, Natthaphat Siri-Angkul, Siriporn Chattipakorn, Nipon Chattipakorn
Sodium-glucose cotransporter 2 inhibitor (SGLT2-i) effects on cardiac ischemia/reperfusion (I/R) injury are unclear. Unlike SGLT2-i, dipeptidyl peptidase 4 inhibitors (DPP4-i) have shown effective cardioprotection in cardiac I/R injury. We aimed to investigate whether SGLT2-i reduces myocardial dysfunction and myocardial injury to a greater extent than DPP4-i in obese-insulin resistant rats with/without cardiac I/R injury. The high fat (HF) diet induced obese-insulin resistant rats were divided into 4 groups and received the following treatments for 28 days: vehicle (HFV); vildagliptin at a dosage of 3 mg/kg/day (HFVil); dapagliflozin at a dosage of 1 mg/kg/day (HFDa); and combination drugs (HFDaVil)...
November 15, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/29138876/lower-risk-of-dementia-with-pioglitazone-compared-with-other-second-line-treatments-in-metformin-based-dual-therapy-a-population-based-longitudinal-study
#8
Chieh-Hsiang Lu, Chen-Yi Yang, Chung-Yi Li, Cheng-Yang Hsieh, Huang-Tz Ou
AIMS/HYPOTHESIS: The effect of pioglitazone was compared with that of other second-line glucose-lowering drugs on the risk of dementia among individuals with type 2 diabetes receiving metformin-based dual therapy. METHODS: A total of 204,323 individuals with type 2 diabetes aged ≥18 years who were stable metformin users and dementia-free before the initiation of second-line glucose-lowering medication were identified in the period 2000-2011 from Taiwan's National Health Insurance Research Database and followed to the end of 2013...
November 14, 2017: Diabetologia
https://www.readbyqxmd.com/read/29136947/the-effect-of-the-dipeptidyl-peptidase-4-inhibitor-sitagliptin-on-gentamicin-nephrotoxicity-in-mice
#9
Yousuf M Al Suleimani, Aly M Abdelrahman, Turan Karaca, Priyadarsini Manoj, Mohammed Ashique, Abderrahim Nemmar, Badreldin H Ali
This study aimed at investigating the possible ameliorative effects of sitagliptin in mice with gentamicin (GEN) nephrotoxicity. Sitagliptin was given to the animals at an oral dose of 10mgkg(-1) per day for 10days, and in some of these mice, GEN was injected intraperitoneally at a dose of 100mgkg(-1) per day during the last seven days of the treatment. Nephrotoxicity was evaluated histopathologically by light microscopy and biochemically by measuring several indices in plasma, urine and renal cortex homogenates...
November 9, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29134608/factors-that-may-account-for-cardiovascular-risk-reduction-with-a-dipeptidyl-peptidase-4-inhibitor-vildagliptin-in-young-patients-with-type-2-diabetes-mellitus
#10
Marc Evans, Plamen Kozlovski, Päivi M Paldánius, James E Foley, Vaishali Bhosekar, Carmen Serban, Angelo Avogaro
INTRODUCTION: In a meta-analysis, we observed a significant 37% relative risk reduction in prospectively adjudicated major adverse cardiac events [MACEs, comprising of non-fatal myocardial infarction, non-fatal stroke, cardiovascular (CV) death] with vildagliptin vs. comparators in younger (< 65 years) patients with type 2 diabetes mellitus (T2DM), while the risk was similar in older patients (≥ 65 years). We carried out an exploratory analysis to identify the patient characteristics and on-treatment effects that may have contributed to the different outcomes in the two age groups...
November 13, 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/29130686/thioamide-substitution-selectively-modulates-proteolysis-and-receptor-activity-of-therapeutic-peptide-hormones
#11
Xing Chen, Elizabeth G Mietlicki-Baase, Taylor M Barrett, Lauren E McGrath, Kieran Koch-Laskowski, John J Ferrie, Matthew R Hayes, E James Petersson
Peptide hormones are attractive as injectable therapeutics and imaging agents, but they often require extensive modification by mutagenesis and/or chemical synthesis to prevent rapid in vivo degradation. Alternatively, the single-atom, O-to-S modification of peptide backbone thioamidation has the potential to selectively perturb interactions with proteases while preserving interactions with other proteins, such as target receptors. Here, we use the validated diabetes therapeutic, glucagon-like peptide-1 (GLP-1), and the target of clinical investigation, gastric inhibitory polypeptide (GIP), as proof-of-principle peptides to demonstrate the value of thioamide substitution...
November 13, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29122893/prospective-postmarketing-surveillance-of-acute-myocardial-infarction-in-new-users-of-saxagliptin-a-population-based-study
#12
Sengwee Toh, Marsha E Reichman, David J Graham, Christian Hampp, Rongmei Zhang, Melissa G Butler, Aarthi Iyer, Malcolm Rucker, Madelyn Pimentel, Jack Hamilton, Samuel Lendle, Bruce H Fireman
OBJECTIVE: The cardiovascular safety of saxagliptin, a dipeptidyl-peptidase 4 inhibitor, compared with other antihyperglycemic treatments is not well understood. We prospectively examined the association between saxagliptin use and acute myocardial infarction (AMI). RESEARCH DESIGN AND METHODS: We identified patients aged ≥18 years, starting from the approval date of saxagliptin in 2009 and continuing through August 2014, using data from 18 Mini-Sentinel data partners...
November 9, 2017: Diabetes Care
https://www.readbyqxmd.com/read/29115211/measurement-of-gastrointestinal-hormones
#13
Nicolai J Wewer Albrechtsen
Towards the end of the 20th century, the number of subjects with diabetes and obesity rose exponentially. The discoveries of insulin- and appetite-modulating chemical signals, including glucagon-like peptide-1 (GLP-1), secreted from the gastrointestinal system, led to development of a new group of drugs which now are being used for glucose-lowering therapy and weight loss. Understanding of the physiology of gut derived signals and their pathophysiologi-cal importance requires accurate measurements of their circulat-ing levels...
November 2017: Danish Medical Journal
https://www.readbyqxmd.com/read/29114002/sdf-1%C3%AE-stromal-cell-derived-factor-1%C3%AE-induces-cardiac-fibroblasts-renal-microvascular-smooth-muscle-cells-and-glomerular-mesangial-cells-to-proliferate-cause-hypertrophy-and-produce-collagen
#14
Edwin K Jackson, Yumeng Zhang, Delbert D Gillespie, Xiao Zhu, Dongmei Cheng, Travis C Jackson
BACKGROUND: Activated cardiac fibroblasts (CFs), preglomerular vascular smooth muscle cells (PGVSMCs), and glomerular mesangial cells (GMCs) proliferate, cause hypertrophy, and produce collagen; in this way, activated CFs contribute to cardiac fibrosis, and activated PGVSMCs and GMCs promote renal fibrosis. In heart and kidney diseases, SDF-1α (stromal cell-derived factor 1α; endogenous CXCR4 [C-X-C motif chemokine receptor 4] receptor agonist) levels are often elevated; therefore, it is important to know whether and how the SDF-1α/CXCR4 axis activates CFs, PGVSMCs, or GMCs...
November 7, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29113797/caveolin-1-a-binding-protein-of-cd26-is-essential-for-the-anti-inflammatory-effects-of-dipeptidyl-peptidase-4-inhibitors-on-human-and-mouse-macrophages
#15
Munenori Hiromura, Kyoko Nohtomi, Yusaku Mori, Hideo Kataoka, Marika Sugano, Kei Ohnuma, Hirotaka Kuwata, Tsutomu Hirano
We previously reported that inhibition of dipeptidyl peptidase (DPP)-4, the catalytic site of CD26, prevents atherosclerosis in animal models through suppression of inflammation; however, the underlying molecular mechanisms have not been fully elucidated. Caveolin-1 (Cav-1), a major structural protein of caveolae located on the surface of the cellular membrane, has been reported to modulate inflammatory responses by binding to CD26 in T cells. In this study, we investigated the role of Cav-1 in the suppression of inflammation mediated by the DPP-4 inhibitor, teneligliptin, using mouse and human macrophages...
November 4, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29113790/the-persistent-inhibitory-properties-of-saxagliptin-on-renal-dipeptidyl-peptidase-4-studies-with-hk-2-cells-in%C3%A2-vitro-and-normal-rats-in%C3%A2-vivo
#16
Masako Uchii, Mariko Sakai, Yuhei Hotta, Satoshi Saeki, Naoya Kimoto, Akinori Hamaguchi, Tetsuya Kitayama, Shunji Kunori
Saxagliptin, a potent and selective DPP-4 inhibitor, exhibits a slow dissociation from DPP-4. We investigated the sustained effects of saxagliptin on renal DPP-4 activity in a washout study using renal tubular (HK-2) cells, and in a pharmacodynamic study using normal rats. In HK-2 cells, the inhibitory potency of saxagliptin on DPP-4 activity persisted after washout, while that of sitagliptin was clearly reduced. In normal rats, a single treatment of saxagliptin or sitagliptin inhibited the plasma DPP-4 activity to similar levels...
October 23, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/29113464/a-new-treatment-strategy-for-parkinson-s-disease-through-the-gut-brain-axis-the-glucagon-like-peptide-1-receptor-pathway
#17
Dong Seok Kim, Ho-Il Choi, Yun Wang, Yu Luo, Barry J Hoffer, Nigel H Greig
Molecular communications in the gut-brain axis, between the central nervous system and the gastrointestinal tract, are critical for maintaining healthy brain function, particularly in aging. Epidemiological analyses indicate type 2 diabetes mellitus (T2DM) is a risk factor for neurodegenerative disorders including Alzheimer's disease (AD) and Parkinson's diseases (PD) for which aging shows a major correlative association. Common pathophysiological features exist between T2DM, AD, and PD, including oxidative stress, inflammation, insulin resistance, abnormal protein processing, and cognitive decline, and suggest that effective drugs for T2DM that positively impact the gut-brain axis could provide an effective treatment option for neurodegenerative diseases...
September 2017: Cell Transplantation
https://www.readbyqxmd.com/read/29110647/a-randomized-placebo-controlled-clinical-trial-evaluating-the-safety-and-efficacy-of-the-once-weekly-dpp-4-inhibitor-omarigliptin-in-patients-with-type-2-diabetes-mellitus-inadequately-controlled-by-glimepiride-and-metformin
#18
Seung-Hwan Lee, Ira Gantz, Elizabeth Round, Melanie Latham, Edward A O'Neill, Paulette Ceesay, Shailaja Suryawanshi, Keith D Kaufman, Samuel S Engel, Eseng Lai
BACKGROUND: Type 2 diabetes (T2D) is a progressive disease that often requires a patient to use multiple antihyperglycemic agents to achieve glycemic control with disease progression. Omarigliptin is a once-weekly dipeptidyl peptidase-4 inhibitor. The purpose of this trial was to assess the efficacy and safety of adding omarigliptin to the treatment regimen of patients with T2D inadequately controlled by dual therapy with metformin and glimepiride. METHODS: Patients with T2D and HbA1c ≥7...
November 6, 2017: BMC Endocrine Disorders
https://www.readbyqxmd.com/read/29109662/budget-impact-of-introducing-linagliptin-into-bosnia-and-herzegovina-health-insurance-drug-reimbursement-list-in-2016-2018
#19
Tarik Catic, Lana Lekic, Vlad Zah, Vedad Tabakovic
Introduction: Diabetes is reaching epidemiological scales worldwide. Beside health implications diabetes bears significant financial impact on health systems. Different treatment options aiming to prevent diabetes complications are available. Dipeptidyl-peptidase-IV (DPP-4) inhibitors like linagliptin are usually add-on therapy to metformin in order to achieve glycemic control. Expenditure for oral antidiabetic medicines in Bosnia and Herzegovina (B&H) is low accounting for only 2.53% of the total drug market expenditure...
September 2017: Materia Socio-medica
https://www.readbyqxmd.com/read/29109299/long-term-trends-in-antidiabetes-drug-usage-in-the-u-s-real-world-evidence-in-patients-newly-diagnosed-with-type-2-diabetes
#20
Olga Montvida, Jonathan Shaw, John J Atherton, Frances Stringer, Sanjoy K Paul
OJBECTIVE: To explore temporal trends in antidiabetes drug (ADD) prescribing and intensification patterns, along with glycemic levels and comorbidities, and possible benefits of novel ADDs in delaying the need for insulin initiation in patients diagnosed with type 2 diabetes. RESEARCH DESIGN AND METHODS: Patients with type 2 diabetes aged 18-80 years, who initiated any ADD, were selected (n = 1,023,340) from the U.S. Centricity Electronic Medical Records. Those who initiated second-line ADD after first-line metformin were identified (subcohort 1, n = 357,482); the third-line therapy choices were further explored...
November 6, 2017: Diabetes Care
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