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Dpp-4 inhibitors

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https://www.readbyqxmd.com/read/29776406/the-effect-of-dpp-4-inhibition-to-improve-functional-outcome-after-stroke-is-mediated-by-the-sdf-1%C3%AE-cxcr4-pathway
#1
Fausto Chiazza, Harald Tammen, Hiranya Pintana, Grazyna Lietzau, Massimo Collino, Thomas Nyström, Thomas Klein, Vladimer Darsalia, Cesare Patrone
BACKGROUND: Dipeptidyl peptidase-4 (DPP-4) inhibitors (gliptins) are approved drugs for the treatment of hyperglycemia in patients with type 2 diabetes. These effects are mainly mediated by inhibiting endogenous glucagon-like peptide-1 (GLP-1) cleavage. Interestingly, gliptins can also improve stroke outcome in rodents independently from GLP1. However, the underlying mechanisms are unknown. Stromal cell-derived factor-1α (SDF-1α) is a DPP-4 substrate and CXCR4 agonist promoting beneficial effects in injured brains...
May 19, 2018: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/29773502/design-synthesis-and-biological-evaluation-of-novel-pyrimidinedione-derivatives-as-dpp-4-inhibitors
#2
Ning Li, Li-Jun Wang, Bo Jiang, Shu-Ju Guo, Xiang-Qian Li, Xue-Chun Chen, Jiao Luo, Chao Li, Yi Wang, Da-Yong Shi
A series of novel pyrimidinedione derivatives were designed and evaluated for in vitro dipeptidyl peptidase-4 (DPP-4) inhibitory activity and in vivo anti-hyperglycemic efficacy. Among them, the representative compounds 11, 15 and 16 showed excellent inhibitory activity of DPP-4 with IC50 values of 64.47 nM, 188.7 nM and 65.36 nM, respectively. Further studies revealed that compound 11 was potent in vivo hypoglycemic effect. The structure-activity relationships of these pyrimidinedione derivatives had been discussed, which would be useful for developing novel DPP-4 inhibitors as treating type 2 diabetes...
May 14, 2018: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29766812/switching-dipeptidyl-peptidase-4-inhibitors-to-tofogliflozin-a-selective-inhibitor-of-sodium-glucose-cotransporter-2-improves-arterial-stiffness-evaluated-by-cardio-ankle-vascular-index-in-patients-with-type-2-diabetes
#3
Nobuhiro Tahara, Sho-Ichi Yamagish, Munehisa Bekki, Atsuko Tahara, Sachiyo Igata, Akihiro Honda, Yoichi Sugiyama, Tomohisa Nakamura, Jiahui Sun, Yuki Kumashiro, Takanori Matsui, Yoshihiro Fukumoto
BACKGROUND: We have found that anagliptin, a dipeptidyl peptidase-4 inhibitor (DPP-4) significantly ameliorates arterial stiffness in type 2 diabetes mellitus (T2DM) patients compared with an equivalent hypoglycemic agent, glimepiride. However, it remains unclear whether and how switching DPP-4 inhibitors to tofogliflozin, a selective inhibitor of sodium-glucose cotransporter 2 (SGLT2) improves arterial stiffness in T2DM patients. METHODS: Nineteen T2DM patients who had received DPP-4 inhibitors for at least 1 year were enrolled in this study...
May 15, 2018: Current Vascular Pharmacology
https://www.readbyqxmd.com/read/29766544/dipeptidyl-peptidase-4-inhibitor-use-is-associated-with-decreased-risk-of-fracture-in-patients-with-type-2-diabetes-a-population-based-cohort-study
#4
Wen-Hsuan Hou, Kai-Cheng Chang, Chung-Yi Li, Huang-Tz Ou
AIMS: To investigate the putative link between dipeptidyl peptidase-4 inhibitor (DPP-4i) use and the risk of fracture in patients with type 2 diabetes. METHODS: This propensity-score-matched population-based cohort study was performed between 2009 and 2013 on patients with type 2 diabetes who were stable metformin users. A total of 3,996 patients with type 2 diabetes used DPP-4i as a second-line antidiabetic drug. The same number of matched non-DPP-4i users were followed up until fracture occurrence, health insurance policy termination, or the end of 2013...
May 16, 2018: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29766510/ineffectiveness-of-saxagliptin-as-a-neuroprotective-drug-in-6-ohda-lesioned-rats
#5
Joelle de Melo Turnes, Taysa Bervian Bassani, Leonardo C Souza, Maria A B F Vital
OBJECTIVES: To determine whether the drug saxagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor which is utilized for the treatment of Diabetes Mellitus, has neuroprotective effects in the animal model of Parkinson's disease (PD) induced by 6-hydroxydopamine (6-OHDA) in rats. METHODS: Male Wistar rats (weighing 280-300 g) received a bilateral infusion of 6-OHDA in the substantia nigra. Twenty-four hours later, they were treated with saxagliptin (1 mg/kg, p.o) once daily, for 21 days...
May 16, 2018: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/29754453/the-dpp-4-inhibitor-anagliptin-ameliorates-hypercholesterolemia-in-hypercholesterolemic-mice-via-inhibition-of-intestinal-cholesterol-transport
#6
Moritaka Goto, Shinji Furuta, Satoko Yamashita, Hiroyuki Hashimoto, Wataru Yano, Noriyuki Inoue, Noriaki Kato, Kohei Kaku
AIMS/INTRODUCTION: Recent data showed that DPP-4 inhibitors exert a lipid-lowering effect in diabetic patients. However, the mechanism of action is not yet clearly understood. We investigated the effect of anagliptin on cholesterol metabolism and transport in the small intestine using non-diabetic hyperlipidemic animals, to clarify the mechanisms underlying the cholesterol-lowering action. MATERIALS AND METHODS: Male ApoE-deficient mice were orally administered anagliptin in the normal chow...
May 13, 2018: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/29752167/dipeptidyl-peptidase-4-inhibitor-use-and-risk-of-diabetic-retinopathy-a-population-based-study
#7
N H Kim, J Choi, N H Kim, K M Choi, S H Baik, J Lee, S G Kim
AIMS: This study examined whether dipeptidyl peptidase (DPP)-4 inhibitor use is beneficial or harmful to diabetic retinopathy (DR) compared with other glucose-lowering agents in patients with type 2 diabetes (T2D). METHODS: From a population-based cohort provided by the National Health Insurance Service in Korea, 67,743 adults with T2D were identified as having been treated with oral glucose-lowering agents between 2008 and 2013. Matching (1:1) was performed for two groups comparing ever-use (cases) and never-use (controls) of DPP-4 inhibitors (n=14,522 in each group)...
March 27, 2018: Diabetes & Metabolism
https://www.readbyqxmd.com/read/29751237/current-anti-diabetic-agents-and-their-molecular-targets-a-review
#8
REVIEW
Nagaraju Kerru, Ashona Singh-Pillay, Paul Awolade, Parvesh Singh
Diabetes mellitus is a medical condition characterized by the body's loss of control over blood sugar. The frequency of diagnosed cases and consequential increases in medical costs makes it a rapidly growing chronic disease that threatens human health worldwide. In addition, its unnerving statistical projections are perilous to both the economy of the nation and man's life expectancy. Type-I and type-II diabetes are the two clinical forms of diabetes mellitus. Type-II diabetes mellitus (T2DM) is illustrated by the abnormality of glucose homeostasis in the body, resulting in hyperglycemia...
May 3, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29748368/cardiovascular-effects-of-new-oral-glucose-lowering-agents-dpp-4-and-sglt-2-inhibitors
#9
REVIEW
André J Scheen
Cardiovascular disease (CVD) is a major challenge in the management of type 2 diabetes mellitus. Glucose-lowering agents that reduce the risk of major cardiovascular events would be considered a major advance, as recently reported with liraglutide and semaglutide, 2 glucagon-like peptide-1 receptor agonists, and with empagliflozin and canagliflozin, 2 SGLT-2 (sodium-glucose cotransporter type 2) inhibitors, but not with DPP-4 (dipeptidyl peptidase-4) inhibitors. The present review is devoted to CV effects of new oral glucose-lowering agents...
May 11, 2018: Circulation Research
https://www.readbyqxmd.com/read/29744822/study-protocol-for-the-initial-choice-of-dpp-4-inhibitor-in-japanese-patients-with-type-2-diabetes-mellitus-effect-of-linagliptin-on-qol-intel-qol-trial
#10
Tomoya Mita, Toru Hiyoshi, Hidenori Yoshii, Hiroko Chimori, Kazuo Ikeda, Junko Sato, Hirotaka Watada
INTRODUCTION: Consideration of treatment-related quality of life (QOL) is important in diabetes management. However, no studies have compared the influence of dipeptidyl peptidase-4 inhibitors versus metformin on treatment-related QOL when used as first-line therapy in patients with type 2 diabetes mellitus. METHODS: This study is a prospective, randomized, open-label, multicenter, parallel-group, comparative study. Between June 2016 and December 2017, 44 participants who failed to achieve glycemic control despite diet and exercise therapy were recruited at 14 clinics and randomly allocated to linagliptin or metformin therapy...
May 9, 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/29740221/effect-of-sitagliptin-on-hepatic-histological-activity-and-fibrosis-of-nonalcoholic-steatohepatitis-patients-a-1-year-randomized-control-trial
#11
Shahinul Alam, Jhumur Ghosh, Golam Mustafa, Mohammad Kamal, Nooruddin Ahmad
Background/purpose: Dipeptidyl peptidase 4 (DPP-4) expression is directly associated with hepatic lipogenesis and liver injury in nonalcoholic steatohepatitis (NASH). This study has been designed to elucidate the histological improvement of NASH with the DPP-4 inhibitor sitagliptin. Materials and methods: In this open-label randomized control trial, paired liver biopsy was taken from 40 NASH patients. Sitagliptin 100 mg was given once daily to the SL group and no sitagliptin was given to the L group for 1 year...
2018: Hepatic Medicine: Evidence and Research
https://www.readbyqxmd.com/read/29731503/evaluation-of-teneligliptin-effects-on-transcriptional-activity-of-ppar%C3%AE-in-cell-based-assays
#12
Yasuhiro Takenaka, Ikuo Inoue, Takanari Nakano, Masaaki Ikeda, Yoshihiko Kakinuma, Yuichi Ikegami, Akira Shimada, Mitsuhiko Noda
BACKGROUND: The antidiabetic drug teneligliptin is a novel dipeptidyl peptidase-4 (DPP-4) inhibitor with a thiazolidine-specific structure. This study aimed to investigate whether teneligliptin can activate PPARγ directly and/or indirectly in cell-based assays. METHODS: Promoter assays using the reporter construct driven under the control of the SV40 promoter and the PPAR response element (PPRE) were performed. Luciferase activity was measured after a 3-day incubation of vector-transduced cells with various concentrations of teneligliptin...
2018: Journal of Nippon Medical School, Nippon Ika Daigaku Zasshi
https://www.readbyqxmd.com/read/29731022/prediabetes
#13
REVIEW
Aditya K Khetan, Sanjay Rajagopalan
The burden of diabetes is expected to rise from 415 million individuals in 2015 to 642 million individuals by 2040. Most individuals pass through a phase of prediabetes before developing full-blown diabetes. Insulin resistance, impaired incretin action, and insulin hypersecretion are central to the pathophysiology of prediabetes. Individuals older than 40 years of age and other high-risk individuals should be screened for diabetes with fasting plasma glucose and/or hemoglobin A1c. For those diagnosed with prediabetes, the goal of treatment should be restoring euglycemia, because there are data showing that restoring normoglycemia during prediabetes and early diabetes can produce lasting remission...
May 2018: Canadian Journal of Cardiology
https://www.readbyqxmd.com/read/29721673/linagliptin-prevents-atrial-electrical-and-structural-remodeling-in-a-canine-model-of-atrial-fibrillation
#14
Tazuru Igarashi, Shinichi Niwano, Hiroe Niwano, Tomoharu Yoshizawa, Hironori Nakamura, Hidehira Fukaya, Tamami Fujiishi, Naruya Ishizue, Akira Satoh, Jun Kishihara, Masami Murakami, Junya Ako
Dipeptidyl peptidase 4 (DPP-4) inhibitors have recently been reported to exhibit additional cardioprotective effects; however, their effect in atrial remodeling, such as in atrial fibrillation (AF), remains unclear. In this study, the effect of linagliptin on atrial electrical and structural remodeling was evaluated in a canine AF model. Sixteen beagle dogs with 3-week atrial rapid stimulation were divided into the linagliptin group (9 mg/kg/day, n = 8) and pacing control group (n = 8). Three additional dogs without rapid pacing were assigned into non-pacing group, which was used as sham in this study...
May 2, 2018: Heart and Vessels
https://www.readbyqxmd.com/read/29715547/anagliptin-inhibits-neointimal-hyperplasia-after-balloon-injury-via-endothelial-cell-specific-modulation-of-sod-1-rhoa-jnk-signaling-in-the-arterial-wall
#15
Qi Li, Mingyu Zhang, Lina Xuan, Yanli Liu, Chang Chen
Intimal hyperplasia is one of the major complications after stenting, but the underlying mechanisms remain unclear. Our previous study found that the dipeptidyl peptidase IV (DPP-4) inhibitor, Anagliptin, suppresses intimal hyperplasia after balloon injury. Here, we further investigated the effects of Anagliptin on endothelial cell (EC) migration after balloon injury. The results showed that Anagliptin administration significantly reduced intimal hyperplasia by stimulating the migration of endothelial cells, but had no effect on the medial area after balloon injury...
April 28, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29713649/treatment-discontinuation-and-clinical-events-in-type-2-diabetes-patients-treated-with-dipeptidyl-peptidase-4-inhibitors-or-nph-insulin-as-third-line-therapy
#16
Cristiano S Moura, Zale B Rosenberg, Michal Abrahamowicz, Sasha Bernatsky, Hassan Behlouli, Louise Pilote
Objective: To compare dipeptidyl peptidase-4 (DPP-4) inhibitors with neutral protamine Hagedorn (NPH) insulin, in terms of effectiveness and safety for the management of patients with type 2 diabetes mellitus (DM2) not controlled on metformin and sulfonylureas. Methods: A retrospective cohort study of individuals with DM2 newly dispensed with either DPP-4 inhibitors or NPH as third-line therapy, after metformin and sulfonylurea. Treatment discontinuation, macrovascular outcomes, and hypoglycemia were compared using multivariable Cox regression models, adjusted for sex, age, year of cohort entry, place of residence, hypertension, past history of hypoglycemia, diabetic ketoacidosis, comorbidities, and number of visits to emergency departments, outpatient physician, and hospitalizations...
2018: Journal of Diabetes Research
https://www.readbyqxmd.com/read/29697017/high-fat-diet-induces-depression-like-behaviour-in-mice-associated-with-changes-in-microbiome-neuropeptide-y-and-brain-metabolome
#17
Ahmed M Hassan, Giulia Mancano, Karl Kashofer, Esther E Fröhlich, Andrija Matak, Raphaela Mayerhofer, Florian Reichmann, Marta Olivares, Audrey M Neyrinck, Nathalie M Delzenne, Sandrine P Claus, Peter Holzer
OBJECTIVES: The biological mechanisms linking diet-related obesity and depression remain unclear. Therefore, we examined the impact of high-fat diet (HFD) on murine behaviour, intestinal microbiome, brain metabolome, neuropeptide Y (NPY) expression, and dipeptidyl peptidase-4 (DPP-4) activity. METHODS: Male C57Bl/6J mice were fed an HFD (60 kJ% from fat) or control diet (12 kJ% from fat) for 8 weeks, followed by behavioural phenotyping. Caecal microbiome was analysed by 16S rDNA sequencing, brain metabolome by 1 H nuclear magnetic resonance, NPY expression by PCR and immunoassay, and dipeptidyl peptidase-4 (DPP-4) activity by enzymatic assay...
April 26, 2018: Nutritional Neuroscience
https://www.readbyqxmd.com/read/29696567/factors-influencing-the-prescribing-preferences-of-physicians-for-drug-naive-patients-with-type-2-diabetes-mellitus-in-the-real-world-setting-in-japan-insight-from-a-web-survey
#18
Hiroki Murayama, Kota Imai, Masato Odawara
INTRODUCTION: The Japanese guidelines for type 2 diabetes mellitus (T2DM) emphasize individualization of treatment based on patient need and encourage physicians to select an appropriate oral antidiabetes drug (OAD). However, limited evidence is available on the factors influencing the selection by physicians (diabetes specialists and nonspecialists) of the first-line OAD to treat drug-naive patients with T2DM. A survey was designed to explore the treatment factors and patient characteristics that influence physicians when they choose an initial OAD to prescribe to a drug-naive patient with T2DM in a real-world setting in Japan...
April 25, 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/29696037/pharmacological-treatment-in-diabetes-mellitus-type-1-insulin-and-what-else
#19
REVIEW
Ewa Otto-Buczkowska, Natalia Jainta
The basis of treatment in autoimmune diabetes is insulin therapy; however, many clinical cases have proven that this method does not solve all problems. Trials of causal treatment including blocking the autoimmune processes and insulin-producing cells transplants were carried out. Those methods require more research to be concerned as efficient and safe ways of treatment in type 1 diabetes. The use of non-insulin adjunct treatment is a new trend. It has been successfully used in laboratories as well as clinical trials...
January 2018: International Journal of Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29682739/bullous-pemphigoid-induced-by-dipeptidyl-peptidase-4-inhibitors-eight-cases-with-clinical-and-immunological-characterization
#20
Irene García-Díez, Marta Ivars-Lleó, Daniel López-Aventín, Norito Ishii, Takashi Hashimoto, Pilar Iranzo, Ramon M Pujol, Agustín España, Josep E Herrero-Gonzalez
BACKGROUND: Dipeptidyl peptidase-4 (DPP-4) inhibitors have increasingly been identified as causative agents of bullous pemphigoid. The clinical and immunological characteristics of this pemphigoid variant are still unclear. The objective of our study was to analyze the clinical and immunological features of patients with pemphigoid induced by DPP-4 inhibitors. METHODS: All patients diagnosed with DPP-4 inhibitor-associated bullous pemphigoid at dermatology departments in three Spanish centers during the period 2013 to 2015 were included...
April 23, 2018: International Journal of Dermatology
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