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dpp4 inhibitor

Sayantan Nath, Sankar Kumar Ghosh, Yashmin Choudhury
INTRODUCTION: A murine model of type 2 diabetes mellitus was used to compare the antidiabetic effects of the dipeptidyl peptidase-4 (DPP4) inhibitor vildagliptin and biguanide, metformin. METHODS: Swiss albino mice (n=20 males; n=25 females) were given high fat diet (HFD) ad libitum for 3weeks followed by low dose (40mgkg(-1) body weight, bw daily) of streptozotocin (STZ) intraperitoneally five times from the 22nd day of treatment onwards, with HFD continued up to 26th day...
October 20, 2016: Journal of Pharmacological and Toxicological Methods
Bhavana Sosale, Aravind R Sosale, Prassanna M Kumar, Shashank R Joshi
BACKGROUND AND AIM: The number of patients with type 2 diabetes (T2DM) is increasing. Most patients with T2DM are uncontrolled and fail to achieve their target Hba1c. In recent years, newer agents such as SGLT2 inhibitors (SGLT2i) have been approved for clinical use. Though data from clinical trials and sub set analysis of Indian patients in global studies are promising, real world evidence from standard clinical practice in India is lacking. The aim of this study was to analyze the metabolic parameters in patients with T2DM on SGLT2i in real world clinical practice...
September 2016: Journal of the Association of Physicians of India
Giulia Cantini, Alessandra Di Franco, Edoardo Mannucci, Michaela Luconi
Glucagon-like peptide 1(9-36) [GLP-1(9-36)] is generated by dipeptidyl peptidase-4 (DPP4) cleavage of the gut incretin hormone, GLP-1(7-36). Since GLP-1(9-36) has a very low affinity for the GLP-1 receptor (GLP-1R), it has so far been considered an inactive form of GLP-1. Here we show GLP-1(9-36) activity in human adipose stem cells (ASC) in vitro. GLP-1(9-36) inhibits human ASC proliferation, glucose uptake and adipogenesis, as well as induces cell apoptosis, to a similar extent as GLP-1(7-36) and liraglutide...
October 13, 2016: Molecular and Cellular Endocrinology
P Sneha, C George Priya Doss
The pace of anti-diabetic drug discovery is very slow in spite of increasing rate of prevalence of Type 2 Diabetes which remains a major public health concern. Though extensive research steps are taken in the past decade, yet craves for better of new treatment strategies to overcome the current scenario. One such general finding is the evolution of gliptins which discriminately inhibits DPP4 (Dipeptidyl peptidase-4) enzyme. Although the mechanism of action of gliptin is highly target oriented and accurate, still its long-term use stands unknown...
October 12, 2016: Life Sciences
Heming Guo, Chen Fang, Yun Huang, Yufang Pei, Linqi Chen, Ji Hu
AIMS: Dipeptidyl peptidase-4 (DPP4) inhibitors are a novel class of antidiabetic medication in the treatment of type 2 diabetes mellitus. Several studies have indicated that DPP4 inhibitors could be used for type 1diabetes (T1DM). Here, we performed a meta-analysis to assess the efficacy and safety of DPP4 inhibitor therapy in patients with T1DM. METHODS: We conducted searches on Medline, Cochrane Library, Web of Science, and EMBASE for relevant studies published before November 21, 2015...
September 28, 2016: Diabetes Research and Clinical Practice
Gemma Pujadas, Daniel J Drucker
Regulatory peptides produced in islet and gut endocrine cells, including glucagon, GLP-1, GLP-2, and GIP exert actions with considerable metabolic importance and translational relevance. Although the clinical development of GLP-1 receptor (GLP-1R) agonists and dipeptidyl peptidase-4(DPP4) inhibitors has fostered research into how these hormones act on the normal and diseased heart, less is known about the actions of these peptides on blood vessels. Here we review the effects of these peptide hormones on normal blood vessels, and highlight their vascular actions in the setting of experimental and clinical vascular injury...
October 12, 2016: Endocrine Reviews
Andrea Egger, Marius E Kraenzlin, Christian Meier
Anti-diabetic drugs are widely used and are essential for adequate glycemic control in patients with type 2 diabetes. Recently, marketed anti-diabetic drugs include incretin-based therapies (GLP-1 receptor agonists and DPP-4 inhibitors) and sodium-glucose co-transporter 2 (SGLT2) inhibitors. In contrast to well-known detrimental effects of thiazolidinediones on bone metabolism and fracture risk, clinical data on the safety of incretin-based therapies is limited. Based on meta-analyses of trials investigating the glycemic-lowering effect of GLP-1 receptor agonists and DPP4 inhibitors, it seems that incretin-based therapies are not associated with an increase in fracture risk...
October 5, 2016: Current Osteoporosis Reports
Dmitri A Pissarnitski, Zhiqiang Zhao, David Cole, Wen-Lian Wu, Martin Domalski, John W Clader, Giovanna Scapin, Johannes Voigt, Aileen Soriano, Theresa Kelly, Mary Ann Powles, Zuliang Yao, Duane A Burnett
Molecular modeling of unbound tricyclic guanine scaffolds indicated that they can serve as effective bioisosteric replacements of xanthines. This notion was further confirmed by a combination of X-ray crystallography and SAR studies, indicating that tricyclic guanine DPP4 inhibitors mimic the binding mode of xanthine inhibitors, exemplified by linagliptin. Realization of the bioisosteric relationship between these scaffolds potentially will lead to a wider application of cyclic guanines as xanthine replacements in drug discovery programs for a variety of biological targets...
November 1, 2016: Bioorganic & Medicinal Chemistry
Karel Vondra
UNLABELLED: Excessive hepatic glucose production resulting from dysregulated glucagon secretion associated with inappropriate fasting and postprandial hyperglucagonemia is common feature in type 2 diabetes (DM2T). The effects of some currently widely used anti-diabetic agents, especially concerning metformin, GLP1 agonists and inhibitors of DPP4, comprise partial supression of glucagon secretion and/or action. Complete supression of glucagon action is recently widely investigated in experiments, and also results of phase 1 and 2 of the clinical trials are available...
2016: Vnitr̆ní Lékar̆ství
Aleš Linhart, Jan Bělohlávek
UNLABELLED: Type 2 diabetes mellitus is associated with a substantial increase in the risk of development of heart failure. The mechanisms causing this complication are complex and include coronary heart disease, myocardial changes induced by hypertension, increased aortic stiffness, arrhythmias, renal failure and last but not least by direct metabolic alterations causing diabetic cardiomyopathy. The heart failure could be induced by several drugs used for diabetes therapy. This review debates the current evidence of harms and benefits of diabetes treatment related to heart failure in the light of results of recent randomized trials...
2016: Vnitr̆ní Lékar̆ství
Makito Tanabe, Ryoko Motonaga, Yuichi Terawaki, Takashi Nomiyama, Toshihiko Yanase
INTRODUCTION: In treatment algorithms of type-2 diabetes mellitus (T2DM) in Western countries, biguanides are recommended as first-line agents. In Japan, various oral hypoglycemic agents (OHAs) are available, but prescription patterns are unclear. MATERIALS AND METHODS: Data of 7,108 and 2,655 T2DM patients in study-1 and -2, respectively, were extracted from the MDV database (2008-2013). Cardiovascular disease (CVD) history was not considered in study-1, but was in study-2...
August 23, 2016: Journal of Diabetes Investigation
Shanta Bhar, Mucheli M V Ramana
With reference to challenges in developing varied and exceedingly complex scaffolds expeditiously through atom economy, domino reactions have assumed a significant role in several transformative endeavors towards established pharmaceuticals and new chemical entities across diverse therapeutic classes such as HIV integrase inhibitors, DPP4 [dipeptidyl peptidase IV] inhibitors, GSK-3 (Glycogen Synthase Kinase 3) inhibitors, neoplastic drugs and microtubule antagonists. The very large chemical space of Domino Reactions can be leveraged for the design strategy of drugs and drug-like candidates with leading examples like Indinavir (Crixivan), Trandolapril (Mavik), Biyouyanagin A, endo pyrrolizidinone diastereomer [GSK] and several others...
August 19, 2016: Current Drug Discovery Technologies
Lorenzo Glorie, Patrick C D'Haese, Anja Verhulst
Dipeptidyl peptidase 4 (DPP4) is a conserved exopeptidase with an important function in protein regulation. The activity of DPP4, an enzyme which can either be anchored to the plasma membrane or circulate free in the extracellular compartment, affects the glucose metabolism, cellular signaling, migration and differentiation, oxidative stress and the immune system. DPP4 is also expressed on the surface of osteoblasts, osteoclasts and osteocytes, and was found to play a role in collagen metabolism. Many substrates of DPP4 have an established role in bone metabolism, among which are incretins, gastrointestinal peptides and neuropeptides...
November 2016: Bone
Friederike Remm, Wolfgang-Michael Franz, Christoph Brenner
Gliptins are accepted as a standard therapy for diabetes mellitus today. By inhibition of the enzyme dipeptidyl peptidase 4 (DPP4), gliptins prolong the GLP1-dependent insulin secretion in the pancreatic β-cells and thus support physiological blood glucose control. Various studies have now raised hope for an additional protective effect of pharmacological DPP4 inhibition in vascular diseases. Besides GLP1, especially, the inhibition of SDF1 cleavage has been shown to depict a relevant mechanism to enhance endothelial regeneration and reduce atherosclerosis progression via the SDF1-CXCR4 axis...
July 2016: European Heart Journal. Cardiovascular Pharmacotherapy
Jixin Zhong, Saumya Kankanala, Sanjay Rajagopalan
PURPOSE OF REVIEW: Atherosclerosis is the leading cause of death globally. The pathophysiology of atherosclerosis is not fully understood. Recent studies suggest dipeptidyl peptidase-4 (DPP4), a regulator of inflammation and metabolism, may be involved in the development of atherosclerotic diseases. Recent advances in the understanding of DPP4 function in atherosclerosis will be discussed in this review. RECENT FINDINGS: Multiple preclinical and clinical studies suggest DPP4/glucagon-like peptide-1 axis is involved in the development of atherosclerotic disease...
October 2016: Current Opinion in Lipidology
Sebastian Steven, Kerstin Jurk, Maximilian Kopp, Swenja Kröller-Schön, Yuliya Mikhed, Kathrin Schwierczek, Siyer Roohani, Fatemeh Kashani, Matthias Oelze, Thomas Klein, Sergey Tokalov, Sven Danckwardt, Susanne Strand, Philip Wenzel, Thomas Münzel, Andreas Daiber
BACKGROUND AND PURPOSE: Excessive inflammation in sepsis causes microvascular thrombosis and thrombocytopenia associated with organ dysfunction and high mortality. The present studies aimed to investigate whether dipeptidyl peptidase-4 (DPP-4) inhibition and supplementation with glucagon-like peptide-1 (GLP-1) analogues improves endotoxaemia-associated microvascular thrombosis via immunomodulatory effects. EXPERIMENTAL APPROACH: Endotoxaemia was induced in C57BL/6 J mice by single injection of lipopolysaccharide (LPS) (17...
July 19, 2016: British Journal of Pharmacology
Mohammad Reza Ashraghi, Gennaro Pagano, Sotirios Polychronis, Flavia Niccolini, Marios Politis
BACKGROUND: Parkinson's disease is a chronic neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons. The pathophysiological mechanisms underlying Parkinson's are still unknown. Mitochondrial dysfunction, abnormal protein aggregation, increased neuroinflammation and impairment of brain glucose metabolism are shared processes among insulin-resistance, diabetes and neurodegeneration and have been suggested as key mechanisms in development of Parkinson's and cognitive impairment...
June 30, 2016: Recent Patents on Endocrine, Metabolic & Immune Drug Discovery
Gianluigi Savarese, Carmen D'Amore, Massimo Federici, Fabiana De Martino, Santo Dellegrottaglie, Caterina Marciano, Francesca Ferrazzano, Teresa Losco, Lars H Lund, Bruno Trimarco, Giuseppe M C Rosano, Pasquale Perrone-Filardi
BACKGROUND: Dipeptidyl Peptidase 4 Inhibitors (DPP4-I) and Sodium-Glucose Linked coTransporter-2 Inhibitors (SGLT2-I) improve glycemic control in patients with type 2 diabetes mellitus (DM). However, only few studies were designed to assess the efficacy and safety of these drugs on cardiovascular (CV) events and mortality. The purpose of the current study was to evaluate the effects of DPP4-Is and SGLT2-Is on CV events and mortality by meta-analysis. METHODS: Randomized trials enrolling more than 200 patients, comparing DPP-4-Is or SGLT2-Is versus placebo or active treatments in patients with DM, and reporting at least one event among all-cause and CV mortality, stroke, myocardial infarction (MI) and new onset of heart failure (HF), were included...
October 1, 2016: International Journal of Cardiology
Choon-Soo Lee, Yun Gi Kim, Hyun-Jai Cho, Jonghanne Park, Heewon Jeong, Sang-Eun Lee, Seung-Pyo Lee, Hyun-Jae Kang, Hyo-Soo Kim
The inhibitors of CD26 (dipeptidyl peptidase-4; DPP4) have been widely prescribed to control glucose level in diabetic patients. DPP4-inhibitors, however, accumulate stromal cell-derived factor-1α (SDF-1α), a well-known inducer of vascular leakage and angiogenesis both of which are fundamental pathophysiology of diabetic retinopathy. The aim of this study was to investigate the effects of DPP4-inhibitors on vascular permeability and diabetic retinopathy. DPP4-inhibitor (diprotin A or sitagliptin) increased the phosphorylation of Src and vascular endothelial-cadherin (VE-cadherin) in human endothelial cells and disrupted endothelial cell-to-cell junctions, which were attenuated by CXCR4 (receptor of SDF-1α)-blocker or Src-inhibitor...
2016: Scientific Reports
I Barchetta, F A Cimini, D Bloise, M G Cavallo
AIMS: Dipeptidyl peptidase-4 inhibitors (DPP4-Is) represent a promising class of agents for type 2 diabetes treatment. Experimental models and clinical studies have reported positive effects of DPP4-Is on bone; however, how DPP4-Is positively impact bone homeostasis in humans remains an unanswered question. Aim of this study investigated the relationship between treatment with DPP4-Is and vitamin D balance in patients with type 2 diabetes. METHODS: This is a cross-sectional study...
October 2016: Acta Diabetologica
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