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https://www.readbyqxmd.com/read/27904111/restoration-of-the-hypothalamic-pituitary-adrenal-response-to-hypoglycemia-in-type-2-diabetes-by-avoiding-chronic-hypoglycemia
#1
Shin-Ichi Tsuda, Kazunori Konishi, Toshiki Otoda, Takako Nagai, Ai Takeda-Watanabe, Megumi Kanasaki, Munehiro Kitada, Atsushi Nakagawa, Makoto Nishizawa, Keizo Kanasaki, Daisuke Koya
An impaired ability to sense and respond to drug-induced hypoglycemia is a common and serious complication in diabetic patients. The hypothalamic-pituitary-adrenal (HPA) axis activity plays a critical role in the counterregulatory response to hypoglycemia. We herein report a case that experienced restoration of a blunted HPA axis by avoiding hypoglycemia with the use of the DPP-4 inhibitor sitagliptin.
2016: Internal Medicine
https://www.readbyqxmd.com/read/27898108/monotreme-glucagon-like-peptide-1-in-venom-and-gut-one-gene-two-very-different-functions
#2
Enkhjargal Tsend-Ayush, Chuan He, Mark A Myers, Sof Andrikopoulos, Nicole Wong, Patrick M Sexton, Denise Wootten, Briony E Forbes, Frank Grutzner
The importance of Glucagon like peptide 1 (GLP-1) for metabolic control and insulin release sparked the evolution of genes mimicking GLP-1 action in venomous species (e.g. Exendin-4 in Heloderma suspectum (gila monster)). We discovered that platypus and echidna express a single GLP-1 peptide in both intestine and venom. Specific changes in GLP-1 of monotreme mammals result in resistance to DPP-4 cleavage which is also observed in the GLP-1 like Exendin-4 expressed in Heloderma venom. Remarkably we discovered that monotremes evolved an alternative mechanism to degrade GLP-1...
November 29, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27895112/hepatic-dipeptidyl-peptidase-4-controls-pharmacokinetics-of-vildagliptin-in-vivo
#3
Mitsutoshi Asakura, Tatsuki Fukami, Miki Nakajima, Hideaki Fujii, Koichiro Atsuda, Tomoo Itoh, Ryoichi Fujiwara
The major metabolic pathway of vildagliptin, which is an inhibitor of dipeptidyl peptidase-4 (DPP-4), in humans is hydrolysis at the cyano group to produce a carboxylic acid metabolite M20.7. Our in vitro study previously demonstrated that DPP-4 itself greatly contributed to the hydrolysis of vildagliptin in mouse, rat, and human livers. To investigate whether hepatic DPP-4 contributes to the hydrolysis of vildagliptin in vivo, in the present study, we conducted in vivo pharmacokinetics studies of vildagliptin in mice co-administered with vildagliptin and sitagliptin, which is another DPP-4 inhibitor, and also in streptozotocin (STZ)-induced diabetic mice...
November 28, 2016: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/27887857/a-potential-contribution-of-dipeptidyl-peptidase-4-by-the-mediation-of-monocyte-differentiation-in-the-development-and-progression-of-abdominal-aortic-aneurysms
#4
Hsin-Ying Lu, Chun-Yao Huang, Chun-Ming Shih, Yi-Wen Lin, Chein-Sung Tsai, Feng-Yen Lin, Chun-Che Shih
OBJECTIVE: Abdominal aortic aneurysms (AAAs) are characterized by the destruction of elastin and collagen in the media and adventitia. Dipeptidyl peptidase-4 (DPP-4, an adipokine known as CD26) influences cell signaling, cell-matrix interactions, and the regulation of the functional activity of incretins in metabolic and inflammatory disorders. Although the role of DPP-4 in AAA evolution has been demonstrated, the underlying mechanisms of DPP-4-regulated AAA development remains unknown...
November 22, 2016: Journal of Vascular Surgery
https://www.readbyqxmd.com/read/27884648/dipeptidyl-peptidase-4-inhibitors-peripheral-arterial-disease-and-lower-extremity-amputation-risk-in-diabetic-patients
#5
Chun-Chin Chang, Yung-Tai Chen, Chien-Yi Hsu, Yu-Wen Su, Chun-Chih Chiu, Hsin-Bang Leu, Po-Hsun Huang, Jaw-Wen Chen, Shing-Jong Lin
BACKGROUND: Recent studies have elucidated the vascular protective effects of dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors). However, to date no large-scale studies have been carried out to determine the impact of DPP-4 inhibitors on the occurrence of peripheral arterial disease, and lower extremity amputation risk in patients with type 2 diabetes mellitus. METHODS: We conducted a retrospective registry analysis using Taiwan's National Health Insurance Research Database to investigate the correlation between the use of DPP-4 inhibitors and risk of peripheral arterial disease in patients with type 2 diabetes mellitus...
November 21, 2016: American Journal of Medicine
https://www.readbyqxmd.com/read/27882332/c-peptide-levels-predict-the-effectiveness-of-dipeptidyl-peptidase-4-inhibitor-therapy
#6
Sevin Demir, Sule Temizkan, Mehmet Sargin
Background. Our aim was to define the conditions that affect therapeutic success when dipeptidyl peptidase-4 (DPP-4) inhibitor is added to metformin monotherapy. Materials and Methods. We reviewed the medical records of 56 patients who had received DPP-4 inhibitor as an add-on to metformin monotherapy and evaluated their response in the first year of therapy. Fasting blood glucose (FBG), HbA1c, C-peptide, and weight of the patients were recorded at 3-month intervals during the first year of treatment. Results...
2016: Journal of Diabetes Research
https://www.readbyqxmd.com/read/27881129/impact-of-dipeptidyl-peptidase-4-inhibitors-on-serum-adiponectin-a-meta-analysis
#7
Xin Liu, Peng Men, Yuhui Wang, Suodi Zhai, George Liu
BACKGROUND: Adiponectin, an adipose-specific protein, is negatively correlated with pro-atherogenic low-density lipoprotein cholesterol (LDL-C) and other cardiovascular risk factors such as insulin resistance. Therefore, low levels of adiponectin are associated with a higher risk for diabetes and cardiovascular disease. Dipeptidyl peptidase-4 inhibitors (DPP4i) have been used for the treatment of type 2 diabetes mellitus (T2DM) as reversible inhibitors through interacting with DPP4 substrate and increase serum incretins such as glucagon-like peptide-1 (GLP-1)...
November 23, 2016: Lipids in Health and Disease
https://www.readbyqxmd.com/read/27875248/vildagliptin-and-caloric-restriction-for-cardioprotection-in-pre-diabetic-rats
#8
Pongpan Tanajak, Hiranya Pintana, Natthaphat Siri-Angkul, Juthamas Khamseekaew, Nattayaporn Apaijai, Siriporn C Chattipakorn, Nipon Chattipakorn
Long-term high-fat diet (HFD) consumption causes cardiac dysfunction. Although calorie restriction (CR) has been shown to be useful in obesity, we hypothesized that combined CR with dipeptidyl peptidase-4 (DPP-4) inhibitor provides greater efficacy than monotherapy in attenuating cardiac dysfunction and metabolic impairment in HFD-induced obese-insulin resistant rats. Thirty male Wistar rats were divided into 2 groups to be fed on either a normal diet (ND, n = 6) or a HFD (n = 24) for 12 weeks. Then, HFD rats were divided into 4 subgroups (n = 6/subgroup) to receive just the vehicle, CR diet (60% of mean energy intake and changed to ND), vildagliptin (3 mg/kg/day) or combined CR and vildagliptin for 4 weeks...
February 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/27873238/cardiovascular-safety-of-dipeptidyl-peptidase-iv-inhibitors-a-meta-analysis-of-placebo-controlled-randomized-trials
#9
Islam Y Elgendy, Ahmed N Mahmoud, Amr F Barakat, Akram Y Elgendy, Marwan Saad, Ahmed Abuzaid, Siddarth A Wayangankar, Anthony A Bavry
BACKGROUND: Large randomized trials have shown conflicting evidence regarding the cardiovascular safety of dipeptidyl-peptidase 4 (DPP-4) inhibitors. Systematic reviews have been limited by incomplete data and inclusion of observational studies. This study aimed to systematically evaluate the cardiovascular safety of DPP-4 inhibitors in patients with type 2 diabetes. METHODS: Electronic databases were searched for randomized trials that compared DPP-4 inhibitors versus placebo and reported cardiovascular outcomes...
November 21, 2016: American Journal of Cardiovascular Drugs: Drugs, Devices, and Other Interventions
https://www.readbyqxmd.com/read/27862902/cardiovascular-events-and-all-cause-mortality-associated-with-sulfonylureas-compared-to-other-antihyperglycaemic-drugs-a-bayesian-meta-analysis-of-survival-data
#10
Steve Bain, Eric Druyts, Chakrapani Balijepalli, Carl A Baxter, Craig Currie, Romita Das, Richard Donnelly, Kamlesh Khunti, Haya Langerman, Paul Leigh, Gaye Siliman, Kristian Thorlund, Kabirraaj Toor, Jiten Vora, Edward J Mills
AIM: Our aim was to conduct a systematic review and meta-analysis to determine the risk of cardiovascular events and all-cause mortality associated with sulfonylureas versus other antihyperglycaemic drugs in patients with type 2 diabetes. MATERIALS AND METHODS: A systematic review of Medline, Embase, Cochrane, and clinicaltrials.gov was conducted comparing sulfonylurea to placebo or other antihyperglycaemic drugs in patients with type 2 diabetes. A cloglog model was employed in the Bayesian framework to obtain comparative hazard ratios between interventions...
November 14, 2016: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/27860391/mechanism-of-lipid-lowering-action-of-the-dpp-4-inhibitor-anagliptin-in-ldlr-deficient-mice
#11
Wataru Yano, Noriyuki Inoue, Shiori Ito, Takahiro Itou, Misako Yasumura, Yasunobu Yoshinaka, Sumihiko Hagita, Moritaka Goto, Takashi Nakagawa, Keisuke Inoue, Sohei Tanabe, Kohei Kaku
AIMS/INTRODUCTION: Dipeptidyl peptidase-4 (DPP-4) inhibitors are used for treatment of patients with type 2 diabetes. In addition to glycemic control, these agents showed beneficial effects on lipid metabolism in clinical trials. However, the mechanism underlying the lipid-lowering effect of DPP-4 inhibitors remains unclear. Here, we investigated the lipid-lowering efficacy of anagliptin in a hyperlipidemic animal model, and examined the mechanism of action. MATERIALS AND METHODS: Male LDLR-deficient mice were administered 0...
November 10, 2016: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/27858848/a-genetic-variant-in-glp1r-is-associated-with-response-to-dpp-4-inhibitors-in-patients-with-type-2-diabetes
#12
Eugene Han, Hye Sun Park, Obin Kwon, Eun Yeong Choe, Hye Jin Wang, Yong-Ho Lee, Sang-Hak Lee, Chul Hoon Kim, Lee-Kyung Kim, Soo Heon Kwak, Kyong Soo Park, Chul Sik Kim, Eun Seok Kang
Incretin hormone-based therapy in type 2 diabetes has been widely used, and dipepdityl peptidase-4 (DPP-4) inhibitors, which prevent incretin degradation, have become popular oral hypoglycemic agents. The efficacy of DPP-4 inhibitors varies from individuals, and factors determining responses to DPP-4 inhibitors have not been fully established. We aimed to investigate whether genetic variations in glucagon-like peptide (GLP-1) receptor are associated with responses to DPP-4 inhibitors in patients with type 2 diabetes...
November 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27852331/energy-restriction-combined-with-dipeptidyl-peptidase-4-inhibitor-exerts-neuroprotection-in-obese-male-rats
#13
Hiranya Pintana, Pongpan Tanajak, Wasana Pratchayasakul, Piangkwan Sa-Nguanmoo, Titikorn Chunchai, Pattarapong Satjaritanun, Linlada Leelarphat, Nipon Chattipakorn, Siriporn C Chattipakorn
Dipeptidyl peptidase-4 (DDP-4) inhibitors and energy restriction (ER) are widely used to treat insulin resistance and type 2 diabetes mellitus. However, the effects of ER or the combination with vildagliptin on brain insulin sensitivity, brain mitochondrial function, hippocampal synaptic plasticity and cognitive function in obese insulin-resistant rats have never been investigated. We hypothesised that ER with DDP-4 inhibitor exerts better efficacy than ER alone in improving cognition in obese insulin-resistant male rats by restoring brain insulin sensitivity, brain mitochondrial function and hippocampal synaptic plasticity...
November 17, 2016: British Journal of Nutrition
https://www.readbyqxmd.com/read/27848150/factors-related-to-the-glucose-lowering-efficacy-of-dipeptidyl-peptidase-4-inhibitors-a-systematic-review-and-meta-analysis-focusing-on-ethnicity-and-study-regions
#14
REVIEW
Kayo Fujita, Masayuki Kaneko, Mamoru Narukawa
BACKGROUND AND OBJECTIVE: Several systematic reviews and meta-analyses have been conducted including an analysis to investigate the difference between ethnic groups in the glucose-lowering efficacy of dipeptidyl peptidase-4 (DPP-4) inhibitors. This study assessed the factors related to the glucose-lowering efficacy and explored potential differences among ethnicities; in particular, Japanese subjects were dealt separately from other Asian subjects. METHODS: A systematic literature search was conducted using the MEDLINE, EMBASE, Cochrane Central Register, Japan Medical Abstracts Society, and ClinicalTrials...
November 16, 2016: Clinical Drug Investigation
https://www.readbyqxmd.com/read/27844335/cardiovascular-safety-of-incretin-based-therapies-in-type-2-diabetes-systematic-review-of-integrated-analyses-and-randomized-controlled-trials
#15
REVIEW
Edoardo Mannucci, Matteo Monami
INTRODUCTION: Regulatory requirements mandate that new drugs for treatment of patients with type 2 diabetes mellitus (T2DM), such as dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists, are evaluated to show that they do not increase cardiovascular (CV) risk. METHODS: A systematic review was undertaken to evaluate the association between DPP-4 inhibitor and GLP-1 receptor agonist use and major adverse cardiac events (MACE)...
November 14, 2016: Advances in Therapy
https://www.readbyqxmd.com/read/27835680/benefits-and-harms-of-sodium-glucose-co-transporter-2-inhibitors-in-patients-with-type-2-diabetes-a-systematic-review-and-meta-analysis
#16
Heidi Storgaard, Lise L Gluud, Cathy Bennett, Magnus F Grøndahl, Mikkel B Christensen, Filip K Knop, Tina Vilsbøll
OBJECTIVE: Sodium-glucose co-transporter 2 inhibitors (SGLT2-i) are a novel drug class for the treatment of diabetes. We aimed at describing the maximal benefits and risks associated with SGLT2-i for patients with type 2 diabetes. DESIGN: Systematic review and meta-analysis. DATA SOURCES AND STUDY SELECTION: We included double-blinded, randomised controlled trials (RCTs) evaluating SGLT2-i administered in the highest approved therapeutic doses (canagliflozin 300 mg/day, dapagliflozin 10 mg/day, and empagliflozin 25 mg/day) for ≥12 weeks...
2016: PloS One
https://www.readbyqxmd.com/read/27835045/cardiovascular-outcomes-of-new-medications-for-type-2-diabetes
#17
Jennifer M Trujillo, Sara A Wettergreen, Wesley A Nuffer, Samuel L Ellis, Michael T McDermott
Cardiovascular (CV) disease remains the leading cause of death in people with diabetes, highlighting the importance of using treatment options that do not increase CV risk or possibly decrease CV outcomes. Since 2008, the Food and Drug Administration has required demonstration of CV safety for all new medications developed for the glycemic management of diabetes. Seven trials have been published that have established CV safety for three DPP-4 inhibitors (alogliptin, saxagliptin, and sitagliptin), three GLP-1 receptor agonists (liraglutide, lixisenatide, and semaglutide), and one sodium-glucose cotransporter-2 inhibitor (empagliflozin)...
November 11, 2016: Diabetes Technology & Therapeutics
https://www.readbyqxmd.com/read/27832184/comparative-binding-analysis-of-dipeptidyl-peptidase-iv-dpp-4-with-antidiabetic-drugs-an-ab-initio-fragment-molecular-orbital-study
#18
Sundaram Arulmozhiraja, Naoya Matsuo, Erika Ishitsubo, Seiji Okazaki, Hitoshi Shimano, Hiroaki Tokiwa
Dipeptidyl peptidase IV (DPP-4) enzyme is responsible for the degradation of incretins that stimulates insulin secretion and hence inhibition of DPP-4 becomes an established approach for the treatment of type 2 diabetics. We studied the interaction between DPP-4 and its inhibitor drugs (sitagliptin 1, linagliptin 2, alogliptin 3, and teneligliptin 4) quantitatively by using fragment molecular orbital calculations at the RI-MP2/cc-pVDZ level to analyze the inhibitory activities of the drugs. Apart from having common interactions with key residues, inhibitors encompassing the DPP-4 active site extensively interact widely with the hydrophobic pocket by their hydrophobic inhibitor moieties...
2016: PloS One
https://www.readbyqxmd.com/read/27820706/dipeptidyl-peptidase-4-inhibition-and-renoprotection-the-role-of-antifibrotic-effects
#19
Yuta Takagaki, Daisuke Koya, Keizo Kanasaki
PURPOSE OF REVIEW: This article analyzes the potential beneficial effects of dipeptidyl peptidase (DPP)-4 inhibitors on renal diseases. RECENT FINDINGS: The pathological significance of DPP-4, either dependent or independent on catalytic activities, on renal diseases has been reported in preclinical studies. With regard to this, we have shown that damaged endothelial cells are converted to a mesenchymal cell phenotype, which is associated with the induction of DPP-4 in endothelial cells...
January 2017: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/27819769/cardiovascular-outcome-trials-of-the-incretin-based-therapies-what-do-we-know-so-far
#20
Pablo F Mora, Eric L Johnson
OBJECTIVE: Diabetes is a well-established pro-inflammatory state with an increased risk for cardiovascular (CV) diseases. In recent years, the number of different classes of agents for the treatment of type 2 diabetes has increased substantially, and while glycemic control is the major focus of these medications, CV safety has become of interest. Two incretin based therapies are currently available, glucagonlike peptide-1 (GLP-1) receptor agonists (RAs) and dipeptidyl peptidase-4 (DPP-4) inhibitors...
November 7, 2016: Endocrine Practice
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