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https://www.readbyqxmd.com/read/29152574/human-intestinal-tract-serves-as-an-alternative-infection-route-for-middle-east-respiratory-syndrome-coronavirus
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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-glycemic-durability-of-dipeptidyl-peptidase-4-inhibitors-and-sulphonylureas-in-patients-with-type-2-diabetes-mellitus-a-meta-analysis-of-long-term-randomized-controlled-trials
#7
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 glycemic durability between dipeptidyl-peptidase 4 (DPP4) inhibitors and sulfonylureas (SUs) in patients with type 2 diabetes mellitus (T2DM), in terms of the changes in glycosylated hemoglobin (HbA1c) levels from an intermediate time point (26 weeks 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
#8
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
#9
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
#10
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...
October 20, 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
#11
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 (DPP4) has been reported to be associated with impairment of insulin signaling in skeletal muscle mass, presumably leading to loss of muscle function. This study was aimed to investigate whether the use of DPP4 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
https://www.readbyqxmd.com/read/29040423/title-therapeutic-strategies-utilising-sdf-1%C3%AE-in-ischaemic-cardiomyopathy
#12
Oliver J Ziff, Daniel I Bromage, Derek M Yellon, Sean M Davidson
Heart failure is rapidly increasing in prevalence and will redraw the global landscape for cardiovascular health. Alleviating and repairing cardiac injury associated with myocardial infarction (MI) is key to improving this burden. Homing signals mobilise and recruit stem cells to the ischaemic myocardium where they exert beneficial paracrine effects. The chemoattractant cytokine SDF-1α and its associated receptor CXCR4 are upregulated after MI and appear to be important in this context. Activation of CXCR4 promotes both cardiomyocyte survival and stem cell migration towards the infarcted myocardium...
October 13, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/29020969/updates-on-cardiovascular-outcome-trials-in-diabetes
#13
REVIEW
Oliver Schnell, Lars Rydén, Eberhard Standl, Antonio Ceriello
In 2008 the Food and Drug Administration introduced a guidance for industry that requires the investigation of cardiovascular outcomes of glucose-lowering medications. Since then, an increasing number of cardiovascular outcome trials have been completed in diabetes patients with high cardiovascular risk for members of the SGLT-2 and DPP4 inhibitors and GLP-1 receptor agonist classes. The trials confirmed cardiovascular safety for all tested anti-hyperglycaemic drugs and, in addition empagliflozin, semaglutide and liraglutide could even reduce cardiovascular risk...
October 11, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28987239/dipeptidyl-peptidase-4-inhibitor-attenuates-obesity-induced-myocardial-fibrosis-by-inhibiting-transforming-growth-factor-%C3%AE-l-and-smad2-3-pathways-in-high-fat-diet-induced-obesity-rat-model
#14
Seul-Ki Hong, Eun-Ho Choo, Sang-Hyun Ihm, Kiyuk Chang, Ki-Bae Seung
Obesity-induced myocardial fibrosis may lead to diastolic dysfunction and ultimately heart failure. Activation of the transforming growth factor (TGF)-βl and its downstream Smad2/3 pathways may play a pivotal role in the pathogenesis of obesity-induced myocardial fibrosis, and the antidiabetic dipeptidyl peptidase 4 inhibitors (DPP4i) might affect these pathways. We investigated whether DPP4i reduces myocardial fibrosis by inhibiting the TGF-β1 and Smad2/3 pathways in the myocardium of a diet-induced obesity (DIO) rat model...
November 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/28966327/dpp4-inhibition-ameliorates-cardiac-function-by-blocking-the-cleavage-of-hmgb1-in-diabetic-mice-after-myocardial-infarction
#15
Akihiko Sato, Satoshi Suzuki, Shunsuke Watanabe, Takeshi Shimizu, Yuichi Nakamura, Tomofumi Misaka, Tetsuro Yokokawa, Tetsuro Shishido, Shu-Ichi Saitoh, Takafumi Ishida, Isao Kubota, Yasuchika Takeishi
High mobility group box 1 (HMGB1), a ubiquitous DNA-binding protein, promotes angiogenesis and tissue repair, resulting in restored cardiac function after myocardial infarction (MI). Although dipeptidyl peptidase 4 (DPP4) degrades certain peptides, it remains unclear as to whether HMGB1 is a substrate of DPP4 and whether DPP4 inhibition prevents the cleavage of HMGB1.In transgenic mice with cardiac-specific overexpression of HMGB1 (TG) and wild-type mice (WT), a diabetic state was induced by streptozotocin, and MI was created by ligation of the left anterior descending coronary artery...
October 21, 2017: International Heart Journal
https://www.readbyqxmd.com/read/28950431/efficacy-and-safety-of-combination-therapy-with-an-alpha-glucosidase-inhibitor-and-a-dipeptidyl-peptidase-4-inhibitor-in-patients-with-type-2-diabetes-mellitus-a-systematic-review-with-meta-analysis
#16
Se Hee Min, Jeong-Hwa Yoon, Seokyung Hahn, Young Min Cho
AIMS/INTRODUCTION: The combination of dipeptidyl peptidase-4 (DPP4) inhibitors and alpha-glucosidase inhibitors (AGIs) may provide an additive or synergistic glucose lowering effect as they have a complementary mode of action. In this study, we examined the efficacy and safety of the addition of a DPP4 inhibitor to patients with type 2 diabetes (T2DM) inadequately controlled with an AGI. MATERIALS AND METHODS: We conducted an electronic search of MEDLINE, EMBASE, the Cochrane Library, and Clinicaltrials...
September 26, 2017: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/28902377/-implementation-of-the-national-guidelines-for-the-treatment-of-diabetes-mellitus-type-2-in-secondary-diabetes-centers
#17
Lydia Marahrens, Daniel Röck, Tjalf Ziemssen, Raimar Kern, Focke Ziemssen, Andreas Fritsche
Background The German National Disease Management Guideline (NVL) on treatment of Type 2 Diabetes recommends lowering of blood glucose in four therapy steps. There is little evidence, how NVL is implemented for the individual patients. Methods 810 patients in secondary diabetes centers were examined within the DiabCheck(OCTplus) trial. Data about the patient's health status (electronic medical record) were classified according to the NVL treatment steps. The degree of implementation was assessed for every person with diabetes type 2 (NCT02 311 504)...
September 2017: Deutsche Medizinische Wochenschrift
https://www.readbyqxmd.com/read/28888840/teneligliptin-prevents-cardiomyocyte-hypertrophy-fibrosis-and-development-of-hypertensive-heart-failure-in-dahl-salt-sensitive-rats
#18
Masayoshi Yamamoto, Tomoko Ishizu, Yoshihiro Seo, Yoshimi Suto, Seika Sai, Dongzhu Xu, Nobuyuki Murakoshi, Taizo Kimura, Yasushi Kawakami, Kazutaka Aonuma
BACKGROUND: We investigated the effects of the dipeptidyl peptidase 4 inhibitor teneligliptin on cardiac function and hemodynamics during heart failure in hypertensive model rats. METHODS AND RESULTS: Fifty-five male Dahl salt-sensitive rats were divided into 4 groups: control group (0.3% NaCl chow; n = 13), hypertension (HT) group (8% NaCl chow; n = 20), HT-early TNL group (8% NaCl chow and teneligliptin from 6 weeks; n = 10), and HT-late TNL group (8% NaCl chow and teneligliptin from 10 weeks; n = 12)...
September 6, 2017: Journal of Cardiac Failure
https://www.readbyqxmd.com/read/28855003/a-review-of-candidate-therapies-for-middle-east-respiratory-syndrome-from-a-molecular-perspective
#19
Ali A Rabaan, Shamsah H Alahmed, Ali M Bazzi, Hatem M Alhani
There have been 2040 laboratory-confirmed cases of Middle East respiratory syndrome coronavirus (MERS-CoV) in 27 countries, with a mortality rate of 34.9 %. There is no specific therapy. The current therapies have mainly been adapted from severe acute respiratory syndrome (SARS-CoV) treatments, including broad-spectrum antibiotics, corticosteroids, interferons, ribavirin, lopinavir-ritonavir or mycophenolate mofetil, and have not been subject to well-organized clinical trials. The development of specific therapies and vaccines is therefore urgently required...
August 31, 2017: Journal of Medical Microbiology
https://www.readbyqxmd.com/read/28853228/comparison-of-effects-of-anagliptin-and-alogliptin-on-serum-lipid-profile-in-type-2-diabetes-mellitus-patients
#20
Akira Kurozumi, Yosuke Okada, Tadashi Arao, Takuya Kobayashi, Daisaku Masuda, Shizuya Yamashita, Yoshiya Tanaka
INTRODUCTION: Anagliptin (ANA) improves dyslipidemia in addition to blood glucose levels. However, there are no comparative studies on the effects of ANA and other dipeptidyl peptidase-4 inhibitors on serum lipid profile. We compared the effects of ANA on serum lipid profile with those of alogliptin (ALO) in type 2 diabetes mellitus outpatients. MATERIALS AND METHODS: The study participants were 87 type 2 diabetes mellitus patients who had been treated with dipeptidyl peptidase-4 inhibitors for ≥8 weeks and had a low-density lipoprotein cholesterol (LDL-C) level of ≥120 mg/dL...
August 29, 2017: Journal of Diabetes Investigation
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