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Dipeptidyl peptidase

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https://www.readbyqxmd.com/read/28334048/hepatoprotective-effect-of-sitagliptin-against-methotrexate-induced-liver-toxicity
#1
Hany M Abo-Haded, Mohamed A Elkablawy, Zeyad Al-Johani, Osama Al-Ahmadi, Dina S El-Agamy
Sitagliptin is selective dipeptidyl peptidase-4 inhibitor (DPP4-I), used clinically as a new oral anti-diabetic agent. This study explored the underlying mechanisms of the hepatoprotective role of sitagliptin pretreatment against methotrexate (MTX) induced hepatotoxicity in mice. Forty mice were divided into four groups (10 mice each); control, MTX, and two sitagliptin groups (pretreated with sitagliptin 10 and 20 mg/kg/day, respectively) for five consecutive days prior to MTX injection. Results showed that MTX induced marked hepatic injury in the form of cloudy swelling, hydropic degeneration, apoptosis and focal necrosis in all hepatic zones...
2017: PloS One
https://www.readbyqxmd.com/read/28333091/marine-peptides-as-potential-agents-for-the-management-of-type-2-diabetes-mellitus-a-prospect
#2
REVIEW
En-Qin Xia, Shan-Shan Zhu, Min-Jing He, Fei Luo, Cheng-Zhan Fu, Tang-Bin Zou
An increasing prevalence of diabetes is known as a main risk for human health in the last future worldwide. There is limited evidence on the potential management of type 2 diabetes mellitus using bioactive peptides from marine organisms, besides from milk and beans. We summarized here recent advances in our understanding of the regulation of glucose metabolism using bioactive peptides from natural proteins, including regulation of insulin-regulated glucose metabolism, such as protection and reparation of pancreatic β-cells, enhancing glucose-stimulated insulin secretion and influencing the sensitivity of insulin and the signaling pathways, and inhibition of bioactive peptides to dipeptidyl peptidase IV, α-amylase and α-glucosidase activities...
March 23, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28332871/sodium-glucose-cotransporter-2-and-dipeptidyl-peptidase-4-inhibition-promise-of-a-dynamic-duo
#3
Ildiko Lingvay
OBJECTIVE: This article reviews evidence supporting sodium glucose cotransporter 2 (SGLT2) inhibitor and dipeptidyl peptidase-4 (DPP-4) inhibitor combination therapy for management of type 2 diabetes mellitus (T2DM). METHODS: We conducted a non-systematic review of the literature focusing on single-pill or fixed-dose combinations of SGLT2 inhibitors and DPP-4 inhibitors available in the United States. RESULTS: SGLT2 inhibitors and DPP-4 inhibitors have complementary mechanisms of action that address several of the underlying pathophysiological abnormalities present in T2DM without overlapping toxicities...
March 23, 2017: Endocrine Practice
https://www.readbyqxmd.com/read/28330582/adipocyte-accumulation-in-the-bone-marrow-during-obesity-and-aging-impairs-stem-cell-based-hematopoietic-and-bone-regeneration
#4
Thomas H Ambrosi, Antonio Scialdone, Antonia Graja, Sabrina Gohlke, Anne-Marie Jank, Carla Bocian, Lena Woelk, Hua Fan, Darren W Logan, Annette Schürmann, Luis R Saraiva, Tim J Schulz
Aging and obesity induce ectopic adipocyte accumulation in bone marrow cavities. This process is thought to impair osteogenic and hematopoietic regeneration. Here we specify the cellular identities of the adipogenic and osteogenic lineages of the bone. While aging impairs the osteogenic lineage, high-fat diet feeding activates expansion of the adipogenic lineage, an effect that is significantly enhanced in aged animals. We further describe a mesenchymal sub-population with stem cell-like characteristics that gives rise to both lineages and, at the same time, acts as a principal component of the hematopoietic niche by promoting competitive repopulation following lethal irradiation...
March 13, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28329747/influence-of-dipeptidyl-peptidase-iv-inhibitor-sitagliptin-on-extracellular-signal-regulated-kinases-1-2-signaling-in-rats-with-diabetic-nephropathy
#5
Xiaojun Ren, Gaohong Liu, Yanhong Wang, Wan Zhang, Fuping Xue, Rongshan Li, Weimin Yu
The protective effects of sitagliptin on the kidneys of rats with diabetic nephropathy (DN) and its influence on extracellular signal-regulated kinases 1/2 (ERK1/2) signaling were investigated. Male Wistar rats (n = 40) were randomly assigned to normal control, DN, low-dose sitagliptin intervention (ST1), or high-dose sitagliptin intervention (ST2) groups. Animals were euthanized after a 16-week treatment, and blood glucose (BG), glycosylated hemoglobin (HbA1c), urinary albumin excretion rate (AER), serum creatinine (Scr), creatinine clearance rate (Ccr), active glucagon-like peptide-1 (GLP-1) levels, kidney hypertrophy index, and renal pathohistology were determined...
March 23, 2017: Pharmacology
https://www.readbyqxmd.com/read/28326532/common-drug-side-effects-and-drug-drug-interactions-in-elderly-adults-in-primary-care
#6
Susan E Merel, Douglas S Paauw
Prescribing medications, recognizing and managing medication side effects and drug interactions, and avoiding polypharmacy are all essential skills in the care of older adults in primary care. Important side effects of medications commonly prescribed in older adults (statins, proton pump inhibitors, trimethoprim-sulfamethoxazole and fluoroquinolone antibiotics, zolpidem, nonsteroidal antiinflammatory drugs, selective serotonin reuptake inhibitors, dipeptidyl peptidase 4 inhibitors) were reviewed. Important drug interactions with four agents or classes (statins, warfarin, factor Xa inhibitors, and calcium channel blockers) are discussed...
March 21, 2017: Journal of the American Geriatrics Society
https://www.readbyqxmd.com/read/28325798/management-of-inpatient-hyperglycemia-and-diabetes-in-older-adults
#7
Guillermo E Umpierrez, Francisco J Pasquel
Adults aged 65 years and older are the fastest growing segment of the U.S. population, and their number is expected to double to 89 million between 2010 and 2050. The prevalence of diabetes in hospitalized adults aged 65-75 years and over 80 years of age has been estimated to be 20% and 40%, respectively. Similar to general populations, the presence of hyperglycemia and diabetes in elderly patients is associated with increased risk of hospital complications, longer length of stay, and increased mortality compared with subjects with normoglycemia...
April 2017: Diabetes Care
https://www.readbyqxmd.com/read/28323503/add-on-dpp-4-inhibitor-alogliptin-alone-or-in-combination-with-pioglitazone-improved-%C3%AE-cell-function-and-insulin-sensitivity-in-metformin-treated-pcos
#8
Mojca Jensterle, Katja Goricar, Andrej Janez
PURPOSE: Impaired β-cell function remains unaddressed in PCOS. The aim of the study was to evaluate whether dipeptidyl peptidase-4 (DPP-4) inhibitor alogliptin (ALO) alone or in combination with pioglitazone (PIO) improves β-cell function along with insulin resistance (IR) in metformin (MET) treated obese women with PCOS with persistent IR. MATERIALS AND METHODS: In 12-week randomized study, ALO 25 mg QD (n=15) or ALO 25 mg QD and PIO 30 mg QD (n=15) was added to MET 1000 mg BID in PCOS women (aged 34...
March 21, 2017: Endocrine Research
https://www.readbyqxmd.com/read/28322746/truncation-of-cxcl12-by-cd26-reduces-its-cxc-chemokine-receptor-4-and-atypical-chemokine-receptor-3-dependent-activity-on-endothelial-cells-and-lymphocytes
#9
Rik Janssens, Anneleen Mortier, Daiane Boff, Pieter Ruytinx, Mieke Gouwy, Bo Vantilt, Olav Larsen, Viktorija Daugvilaite, Mette M Rosenkilde, Marc Parmentier, Sam Noppen, Sandra Liekens, Jo Van Damme, Sofie Struyf, Mauro M Teixeira, Flávio A Amaral, Paul Proost
The chemokine CXCL12 or stromal cell-derived factor 1/SDF-1 attracts hematopoietic progenitor cells and mature leukocytes through the G protein-coupled CXC chemokine receptor 4 (CXCR4). In addition, it interacts with atypical chemokine receptor 3 (ACKR3 or CXCR7) and glycosaminoglycans. CXCL12 activity is regulated through posttranslational cleavage by CD26/dipeptidyl peptidase 4 that removes two N-terminal amino acids. CD26-truncated CXCL12 does not induce calcium signaling or chemotaxis of mononuclear cells...
March 16, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28322294/effects-of-dipeptidyl-peptidase-4-inhibitors-on-beta-cell-function-and-insulin-resistance-in-type-2-diabetes-meta-analysis-of-randomized-controlled-trials
#10
Xiafei Lyu, Xiaolin Zhu, Bin Zhao, Liang Du, Dawei Chen, Chun Wang, Guanjian Liu, Xingwu Ran
Dipeptidyl peptidase-4 (DPP-4) inhibitors are a novel family of glucose-lowering agents. Accumulating evidence suggests that DPP-4 inhibitors preserve pancreatic beta-cell function, but results in previous studies have been inconsistent. We assessed the effects of DPP-4 inhibitors on the homoeostasis model assessment beta-cell function (HOMA-B) or insulin resistance (HOMA-IR) index in patients with type 2 diabetes through a systematic review and meta-analysis of randomized controlled trials (RCTs). Relevant articles were identified from PubMed, Embase, and Cochrane Library databases up to December 27, 2016...
March 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28322073/sglt2-inhibitor-dpp-4-inhibitor-combination-therapy-complementary-mechanisms-of-action-for-management-of-type-2-diabetes-mellitus
#11
Jayant Dey
Type 2 diabetes mellitus is a progressive disease with multiple underlying pathophysiologic defects. Monotherapy alone cannot maintain glycemic control and leads to treatment failure. Ideally, a combination of glucose-lowering agents should have complementary mechanisms of action that address multiple pathophysiologic pathways, can be used at all stages of the disease, and be generally well tolerated with no increased risk of hypoglycemia, cardiovascular events, or weight gain. The combination should also provide conveniences for patients, such as oral dosing, single-pill formulations, and once-daily administration, potentially translating to improved adherence...
March 21, 2017: Postgraduate Medicine
https://www.readbyqxmd.com/read/28321057/the-glucose-lowering-efficacy-of-sitagliptin-in-obese-japanese-patients-with-type-2-diabetes
#12
Ryo Kodera, Kenichi Shikata, Akihiko Nakamura, Satoru Okazaki, Ryo Nagase, Tatsuaki Nakatou, Shigeru Haisa, Kazuyuki Hida, Katsuhiro Miyashita, Hirofumi Makino
Objective Dipeptidyl peptidase-4 (DPP-4) inhibitors are the most frequently prescribed oral hypoglycemic agents in Japan. Although a relationship between the efficacy of DPP-4 inhibitors and the body mass index (BMI) has been reported, this relationship is controversial. We investigated whether the BMI value affects the glucose-lowering efficacy of sitagliptin in obese Japanese patients with type 2 diabetes. Methods One hundred sixty-two outpatients with inadequate glycemic control were divided into four groups based on their baseline BMI values...
2017: Internal Medicine
https://www.readbyqxmd.com/read/28318663/dipeptidyl-peptidase-iv-in-chronic-heart-failure-with-reduced-ejection-fraction
#13
Patrícia Lourenço, Sérgio Silva, Filipe Cunha, Joana Pereira, Ana Ribeiro, Nuno Silva, João Tiago Guimarães, José Paulo Araújo, Paulo Bettencourt
BACKGROUND: An association between dipeptidyl peptidase-IV (DPP-IV) inhibitors with worse prognosis in HF has been suggested. We aimed to assess the serum DPP-IV levels in chronic stable HF patients and determine their association with prognosis. METHODS AND RESULTS: Chronic stable HF patients with optimized prognostic-modifying therapy were prospectively recruited. EXCLUSION CRITERIA: 1) ejection fraction>50%, 2) hospitalizations or therapeutic adjustments in the previous 2months; 3) patients on renal replacement therapy, and 4) use of DPP-IV inhibitors...
March 11, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28314484/impact-of-health-policy-and-practice-on-finding-the-best-fit-for-patients-with-type-2-diabetes-after-metformin-failure-croatian-pilot-study
#14
Maja Cigrovski Berković, Davorka Herman Mahečić, Marina Gradišer, Ines Bilić-Ćurčić
AIM: We assessed the impact of clinical practice and health policy on the choice and efficacy of different second-line therapies for the treatment of type 2 diabetes (T2DM) after failure of metformin. METHODS: This retrospective database analysis included 200 patients with a follow-up period of 6 months. The primary end-point was achievement of HbA1c <7% and fasting (FBG) and postprandial glucose levels (PPG) <7.2mmol/L and <10mmol/L, respectively after three and six months of different add-on treatments...
March 14, 2017: Primary Care Diabetes
https://www.readbyqxmd.com/read/28302310/design-synthesis-and-anti-diabetic-activity-of-triazolotriazine-derivatives-as-dipeptidyl-peptidase-4-dpp-4-inhibitors
#15
Bhumika D Patel, Shraddha V Bhadada, Manjunath D Ghate
Type 2 diabetes mellitus (T2DM) is one of the major global metabolic disorders characterized by insulin resistance and chronic hyperglycemia. Inhibition of the enzyme, dipeptidyl peptidase-4 (DPP-4) has been proved as successful and safe therapy for the treatment of T2DM since last decade. In order to design novel DPP-4 inhibitors, various in silico studies such as 3D-QSAR, pharmacophore modeling and virtual screening were performed and on the basis of the combined results of them, total 50 triazolo[5,1-c][1,2,4]triazine derivatives were designed and mapped on the best pharmacophore model...
March 6, 2017: Bioorganic Chemistry
https://www.readbyqxmd.com/read/28296349/dipeptidyl-peptidase-4-inhibitors-as-preferable-oral-hypoglycemic-agents-in-terms-of-treatment-satisfaction-results-from-a-multicenter-12-week-open-label-randomized-controlled-study-in-japan
#16
Hitoshi Ishii, Yasuaki Hayashino, Yasuhiro Akai, Matahiro Yabuta, Satoru Tsujii
AIMS/INTRODUCTION: To compare the treatment satisfaction of four classes of oral hypoglycemic agents (OHAs): dipeptidyl peptidase-4 (DPP-4) inhibitors, α-glucosidase inhibitors (αGI), biguanides (BG), and sulfonylureas (SU), which are common initial treatments for type 2 diabetes mellitus patients in Japan, and to identify the best OHA in terms of treatment satisfaction. MATERIALS AND METHODS: In this 12-week, randomized, controlled, open-label study, Japanese outpatients with type 2 diabetes mellitus who were naïve to pharmacological treatment were randomly assigned a DPP-4 inhibitor, a BG, an αGI, or a SU...
March 14, 2017: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/28295491/national-trends-in-the-treatment-of-diabetic-nephropathy-in-the-united-states
#17
O Ajiboye, J B Segal
WHAT IS KNOWN AND OBJECTIVE: The prevalence of diabetic nephropathy continues to rise and it remains a strong predictor of morbidity and mortality in diabetic patients. Patients diagnosed with diabetic nephropathy are actively excluded from most trials involving diabetic medications and it is important to understand the prescription patterns in this subset of patients with diabetes. METHODS: Using the IMS Health's National Disease and Therapeutic Index, we analysed the medication prescription patterns for six classes of medications from 2010 to 2014 among patients, 35 years or older, with diabetic nephropathy...
March 15, 2017: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/28292762/gpr40-reduces-food-intake-and-body-weight-through-glp-1
#18
Judith N Gorski, Michele J Pachanski, Joel Mane, Christopher W Plummer, Sarah Souza, Brande S Thomas-Fowlkes, Aimie M Ogawa, Adam B Weinglass, Jerry Di Salvo, Boonlert Cheewatrakoolpong, Andrew D Howard, Steven L Colletti, Maria E Trujillo
GPR40 partial agonists lower glucose through the potentiation of glucose-stimulated insulin secretion, which is believed to provide significant glucose lowering without the weight gain or hypoglycemic risk associated with exogenous insulin or glucose independent insulin secretagogues. The class of small molecule GPR40 modulators, known as AgoPAMs (agonist also capable of acting as positive allosteric modulators), differentiate from partial agonists, binding to a distinct site and functioning as full agonists to stimulate the secretion of both insulin and GLP-1 (17)...
March 14, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28292575/the-treatment-of-type-2-diabetes-mellitus-in-patients-with-chronic-kidney-disease-what-to-expect-from-new-oral-hypoglycemic-agents
#19
REVIEW
Luca Di Lullo, Michela Mangano, Claudio Ronco, Vincenzo Barbera, Antonio De Pascalis, Antonio Bellasi, Domenico Russo, Biagio Di Iorio, Mario Cozzolino
Worldwide, an estimated 200 million people have chronic kidney disease (CKD), whose most common causes include hypertension, arteriosclerosis, and diabetes. About 40% of patients with diabetes develop CKD and intensive blood glucose control through pharmacological intervention can delay CKD progression. Standard therapies for the treatment of type 2 diabetes mellitus include metformin, sulfonylureas, meglitinides, thiazolidinediones, and insulin. While these drugs have an important role in the management of type 2 diabetes, only the thiazolidinedione pioglitazone can be used across the spectrum of CKD (stages 2-5) and without dose adjustment...
March 6, 2017: Diabetes & Metabolic Syndrome
https://www.readbyqxmd.com/read/28291655/the-cardiovascular-safety-trials-of-dpp-4-inhibitors-glp-1-agonists-and-sglt2-inhibitors
#20
REVIEW
Matthew H Secrest, Jacob A Udell, Kristian B Filion
In this paper, we review the results of large, double-blind, placebo-controlled randomized trials mandated by the US Food and Drug Administration to examine the cardiovascular safety of newly-approved antihyperglycemic agents in patients with type 2 diabetes. The cardiovascular effects of dipeptidyl peptidase-4 (DPP-4) inhibitors remain controversial: while these drugs did not reduce or increase the risk of primary, pre-specified composite cardiovascular outcomes, one DPP-4 inhibitor (saxagliptin) increased the risk of hospitalization for heart failure in the overall population; another (alogliptin) demonstrated inconsistent effects on heart failure hospitalization across subgroups of patients, and a third (sitagliptin) demonstrated no effect on heart failure...
January 28, 2017: Trends in Cardiovascular Medicine
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