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https://www.readbyqxmd.com/read/29331088/significance-of-circulatory-dpp4-activity-in-metabolic-diseases
#1
REVIEW
Titli Nargis, Partha Chakrabarti
Dipeptidyl peptidase 4 (DPP4), also known as CD26 is a type II transmembrane protein that is released from the cell membrane in a nonclassical secretory mechanism. This exopeptidase selectively degrades varieties of substrates including incretin hormones, growth factors, and cytokines. A significant detectable amount of DPP4 activity can be measured in plasma as well as in different tissues such as intestinal epithelium, vascular endothelium, lymphocytes, monocytes, kidney, liver, adipose, lung, thymus, spleen, prostate, etc...
January 13, 2018: IUBMB Life
https://www.readbyqxmd.com/read/29320602/when-metformin-is-not-enough-pros-and-cons-of-sglt2-and-dpp-4-inhibitors-as-a-second-line-therapy
#2
REVIEW
Angelo Avogaro, Elías Delgado, Ildiko Lingvay
The newer oral therapies for type 2 diabetes (T2DM); dipeptidyl peptidase-4 (DPP-4) inhibitors and sodium glucose cotransporter 2 (SGLT2) inhibitors have advantages over older agents. DPP-4 inhibitors are weight neutral, and have few adverse effects. SGLT2 inhibitors have additional benefits; weight loss, blood pressure reduction, cardiovascular risk reduction, and renoprotective effects. SGLT2 inhibitors, have increased risk of urogenital infections and possible risk of "euglycaemic" diabetic ketoacidosis...
January 10, 2018: Diabetes/metabolism Research and Reviews
https://www.readbyqxmd.com/read/29289540/a-randomized-controlled-study-comparing-a-dpp4-inhibitor-linagliptin-and-basal-insulin-glargine-in-patients-with-type-2-diabetes-in-long-term-care-and-skilled-nursing-facilities-linagliptin-ltc-trial
#3
Guillermo E Umpierrez, Saumeth Cardona, David Chachkhiani, Maya Fayfman, Sahebi Saiyed, Heqiong Wang, Priyathama Vellanki, J Sonya Haw, Darin E Olson, Francisco J Pasquel, Theodore M Johnson
OBJECTIVES: Safe and easily implemented treatment regimens are needed for the management of patients with type 2 diabetes mellitus (T2DM) in long-term care (LTC) and skilled nursing facilities. DESIGN: This 6-month open-label randomized controlled trial compared the efficacy and safety of a DPP4 inhibitor (linagliptin) and basal insulin (glargine) in LTC residents with T2DM. SETTINGS: Three LTC institutions affiliated with a community safety-net hospital, US Department of Veterans Affairs and Emory Healthcare System in Atlanta, Georgia...
December 27, 2017: Journal of the American Medical Directors Association
https://www.readbyqxmd.com/read/29242380/insights-into-the-proteome-of-gastrointestinal-stromal-tumors-derived-exosomes-reveals-new-potential-diagnostic-biomarkers
#4
Safinur Atay, Daniel W Wilkey, Mohammed M Milhem, Michael Merchant, Andrew K Godwin
Developing tumors continuously release nano-sized vesicles that represent circulating "fingerprints" of the tumor's identity.  In gastrointestinal stromal tumor (GIST), we have previously reported that these tumors release "oncosomes" carrying the constitutively activated tyrosine kinase (TK) receptor KIT.  Despite the clinical utility of TK inhibitors, such as imatinib mesylate (IM), recurrence and metastasis are clinical problems that urge the need to identify new tumor-derived molecules.  To this aim, we performed the first high quality proteomic study of GIST-derived exosomes (GDEs) and identified 1,060 proteins composing the core GDE proteome (cGDEp)...
December 14, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29231750/concordance-with-prescribing-information-dosage-recommendations-for-dipeptidyl-peptidase-4-inhibitors-among-type-2-diabetes-mellitus-patients-with-moderate-to-severe-chronic-kidney-disease
#5
Huan Huang, Sharash Shetty, Elise Bauer, Kathleen Lang
OBJECTIVE: To estimate the proportion of patients with moderate to severe chronic kidney disease (CKD) whose initial DPP4-i dosage was concordant with prescribing information (label) recommendations in the United States. METHODS: Adult patients with T2DM who initiated a DPP4-i (linagliptin, sitagliptin, saxagliptin) between Jan 1, 2011 and Jun 30, 2014 were identified using electronic medical records and administrative claims, with index date being the date of first observed DPP4-i treatment...
December 12, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/29203510/mechanisms-to-elevate-endogenous-glucagon-like-peptide-1-glp-1-beyond-injectable-glp-1-analogues-and-metabolic-surgery
#6
Daniel A Briere, Ana B Bueno, Ellen J Gunn, M Dodson Michael, Kyle W Sloop
Therapeutic engineering of glucagon-like peptide-1 (GLP-1) has enabled development of new medicines to treat type 2 diabetes mellitus. These injectable analogues achieve robust glycemic control by increasing concentrations of 'GLP-1 equivalents' (∼50 pM). Similar levels of endogenous GLP-1 occur following gastric bypass surgery, and mechanistic studies indicate glucose lowering by these procedures is driven by GLP-1. Therefore, due to the remarkable signaling and secretory capacity of the GLP-1 system, we sought to discover mechanisms that raise GLP-1 pharmacologically...
December 4, 2017: Diabetes
https://www.readbyqxmd.com/read/29200879/cost-consequence-analysis-of-sitagliptin-versus-sulfonylureas-as-add-on-therapy-for-the-treatment-of-diabetic-patients-in-italy
#7
Valentina Lorenzoni, Fabio Baccetti, Stefano Genovese, Enrico Torre, Giuseppe Turchetti
Objective: Diabetes mellitus is a chronic disease related to a significant impact in both epidemiologic and economic terms. In Italy, around 3.6 million people are affected by diabetes and this number is expected to increase significantly in the next few years. As recommended by current national and international guidelines, metformin (Met) is prescribed as first-line pharmacological treatment, and many pharmacological alternatives are available for patients uncontrolled with Met monotherapy...
2017: ClinicoEconomics and Outcomes Research: CEOR
https://www.readbyqxmd.com/read/29171700/practical-strategies-for-improving-outcomes-in-t2dm-the-potential-role-of-pioglitazone-and-dpp4-inhibitors
#8
REVIEW
Stefano Del Prato, Robert Chilton
T2DM is a complex disease underlined by multiple pathogenic defects responsible for the development and progression of hyperglycaemia. Each of these factors can now be tackled in a more targeted manner thanks to glucose-lowering drugs that have been made available in the past 2 to 3 decades. Recognition of the multiplicity of the mechanisms underlying hyperglycaemia calls for treatments that address more than 1 of these mechanisms, with more emphasis placed on the earlier use of combination therapies. Although chronic hyperglycaemia contributes to and amplifies cardiovascular risk, several trials have failed to show a marked effect from intensive glycaemic control...
November 24, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29170542/diabetes-metformin-a-cardiovascular-moderator-of-dpp4-inhibitors
#9
André J Scheen
No abstract text is available yet for this article.
January 2018: Nature Reviews. Endocrinology
https://www.readbyqxmd.com/read/29152574/human-intestinal-tract-serves-as-an-alternative-infection-route-for-middle-east-respiratory-syndrome-coronavirus
#10
Jie Zhou, Cun Li, Guangyu Zhao, Hin Chu, Dong Wang, Helen Hoi-Ning Yan, Vincent Kwok-Man Poon, Lei Wen, Bosco Ho-Yin Wong, Xiaoyu Zhao, Man Chun Chiu, Dong Yang, Yixin Wang, Rex K H Au-Yeung, Ivy Hau-Yee Chan, Shihui Sun, Jasper Fuk-Woo Chan, Kelvin Kai-Wang To, Ziad A Memish, Victor M Corman, Christian Drosten, Ivan Fan-Ngai Hung, Yusen Zhou, Suet Yi Leung, Kwok-Yung Yuen
Middle East respiratory syndrome coronavirus (MERS-CoV) has caused human respiratory infections with a high case fatality rate since 2012. However, the mode of virus transmission is not well understood. The findings of epidemiological and virological studies prompted us to hypothesize that the human gastrointestinal tract could serve as an alternative route to acquire MERS-CoV infection. We demonstrated that human primary intestinal epithelial cells, small intestine explants, and intestinal organoids were highly susceptible to MERS-CoV and can sustain robust viral replication...
November 2017: Science Advances
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
#11
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
#12
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/29135080/a-comparison-of-adherence-and-persistence-by-medication-class-in-type-2-diabetes-a-systematic-review-and-meta-analysis
#13
Andrew McGovern, Zayd Tippu, William Hinton, Neil Munro, Martin Whyte, Simon de Lusignan
Limited medication adherence and persistence are barriers to successful treatment in type 2 diabetes (T2D). We searched MEDLINE, EMBASE, The Cochrane Library, The Register of Controlled Trials, PsychINFO, and CINAHL for observational and interventional studies comparing medication adherence or persistence between two or more glucose lowering medications in people with T2D. Where several studies (n≥5) provided the same comparison a random effects meta-analysis was performed reporting mean difference (MD), odds ratio (OR), or hazard ratio (HR) depending on the pooled study outcomes...
November 14, 2017: Diabetes, Obesity & Metabolism
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/29107298/klk5-induces-shedding-of-dpp4-from-circulatory-th17-cells-in-type-2-diabetes
#15
Titli Nargis, Krishna Kumar, Amrit Raj Ghosh, Amit Sharma, Dipayan Rudra, Debrup Sen, Saikat Chakrabarti, Satinath Mukhopadhyay, Dipyaman Ganguly, Partha Chakrabarti
OBJECTIVE: Increasing plasma levels and activity of dipeptidyl peptidase-4 (DPP4 or CD26) are associated with rapid progression of metabolic syndrome to overt type 2 diabetes mellitus (T2DM). While DPP4 inhibitors are increasingly used as anti-hyperglycemic agents, the reason for the increase in plasma DPP4 activity in T2DM patients remains elusive. METHODS: We looked into the source of plasma DPP4 activity in a cohort of 135 treatment naive nonobese (BMI < 30) T2DM patients...
November 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29095568/direct-head-to-head-comparison-of-glycaemic-durability-of-dipeptidyl-peptidase-4-inhibitors-and-sulphonylureas-in-patients-with-type-2-diabetes-mellitus-a-meta-analysis-of-long-term-randomized-controlled-trials
#16
Kang Chen, Deying Kang, Miao Yu, Ruya Zhang, Ye Zhang, Guojuan Chen, Yiming Mu
We performed a meta-analysis of randomized controlled trials (RCTs) to compare the long-term glycaemic durability of dipeptidyl-peptidase 4 (DPP-4) inhibitors vs that of sulphonylureas (SUs) in patients with type 2 diabetes mellitus (T2DM), in terms of the changes in glycated haemoglobin (HbA1c) levels from an intermediate time point (26 or 52 weeks) to 104 weeks of treatment. The Medline (PubMed), Embase (Ovid), and CENTER (Cochrane Library) databases were searched for relevant RCTs. Eight RCTs were included...
November 2, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29093273/genetic-determinants-of-circulating-gip-and-glp-1-concentrations
#17
Peter Almgren, Andreas Lindqvist, Ulrika Krus, Liisa Hakaste, Emilia Ottosson-Laakso, Olof Asplund, Emily Sonestedt, Rashmi B Prasad, Esa Laurila, Marju Orho-Melander, Olle Melander, Tiinamaija Tuomi, Jens Juul Holst, Peter M Nilsson, Nils Wierup, Leif Groop, Emma Ahlqvist
The secretion of insulin and glucagon from the pancreas and the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) from the gastrointestinal tract is essential for glucose homeostasis. Several novel treatment strategies for type 2 diabetes (T2D) mimic GLP-1 actions or inhibit incretin degradation (DPP4 inhibitors), but none is thus far aimed at increasing the secretion of endogenous incretins. In order to identify new potential therapeutic targets for treatment of T2D, we performed a meta-analysis of a GWAS and an exome-wide association study of circulating insulin, glucagon, GIP, and GLP-1 concentrations measured during an oral glucose tolerance test in up to 7,828 individuals...
November 2, 2017: JCI Insight
https://www.readbyqxmd.com/read/29071110/real-world-weight-change-among-patients-treated-with-glucagon-like-peptide-1-receptor-agonist-dipeptidyl-peptidase-4-inhibitor-and-sulfonylureas-for-type-2-diabetes-and-the-influence-of-medication-adherence
#18
G S Carls, R Tan, J Y Zhu, E Tuttle, J Yee, S V Edelman, W H Polonsky
AIMS: The study aims to examine real-world weight change and the role of medication adherence among patients with type 2 diabetes who initiated one of three drug classes: glucagon-like peptide-1 receptor agonist (GLP-1RA), dipeptidyl peptidase-4 inhibitor (DPP4) and sulfonylureas (SUs). MATERIALS AND METHODS: A cohort of patients initiating one of the three drug classes was selected from a large US database of integrated electronic medical record and administrative claims...
September 2017: Obesity Science & Practice
https://www.readbyqxmd.com/read/29061303/unique-binding-mode-of-evogliptin-with-human-dipeptidyl-peptidase-iv
#19
Hyung Ki Lee, Mi-Kyung Kim, Ha Dong Kim, Heung Jae Kim, Ji Won Kim, Jie-Oh Lee, Chan-Wha Kim, Eunice EunKyeong Kim
Evogliptin ((R)-4-((R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl)-3-(tert-butoxymethyl) piperazine-2-one)) is a highly potent selective inhibitor of dipeptidyl peptidase IV (DPP4) that was approved for the treatment of type 2 diabetes in South Korea. In this study, we report the crystal structures of Evogliptin, DA-12166, and DA-12228 (S,R diastereomer of Evogliptin) complexed to human DPP4. Analysis of both the structures and inhibitory activities suggests that the binding of the trifluorophenyl moiety in the S1 pocket and the piperazine-2-one moiety have hydrophobic interactions with Phe357 in the S2 extensive subsite, and that the multiple hydrogen bonds made by the (R)-β-amine group in the S2 pocket and the contacts made by the (R)-tert-butyl group with Arg125 contribute to the high potency observed for Evogliptin...
December 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29054111/dipeptidyl-peptidase-4-inhibitors-attenuates-the-decline-of-skeletal-muscle-mass-in-patients-with-type-2-diabetes
#20
Ryotaro Bouchi, Tatsuya Fukuda, Takato Takeuchi, Yujiro Nakano, Masanori Murakami, Isao Minami, Hajime Izumiyama, Koshi Hashimoto, Takanobu Yoshimoto, Yoshihiro Ogawa
BACKGROUND: Activation of dipeptidyl peptidase 4 has been reported to be associated with impairment of insulin signalling in skeletal muscle, presumably leading to loss of muscle function. This study was aimed to investigate whether the use of dipeptidyl peptidase 4 inhibitors (DPP4i) could attenuate the progressive loss of muscle mass in patients with type 2 diabetes. METHODS: A total 105 patients with type 2 diabetes (mean age 62 ± 12 years; 39% female) were studied in this retrospective observational study...
October 20, 2017: Diabetes/metabolism Research and Reviews
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