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Peptidase inhibitor

Devin Abrahami, Antonios Douros, Hui Yin, Oriana Hoi Yun Yu, Christel Renoux, Alain Bitton, Laurent Azoulay
OBJECTIVE: To assess whether the use of dipeptidyl peptidase-4 inhibitors is associated with the incidence of inflammatory bowel disease in patients with type 2 diabetes. DESIGN: Population based cohort study. SETTING: More than 700 general practices contributing data to the United Kingdom Clinical Practice Research Datalink. PARTICIPANTS: A cohort of 141 170 patients, at least 18 years of age, starting antidiabetic drugs between 1 January 2007 and 31 December 2016, with follow-up until 30 June 2017...
March 21, 2018: BMJ: British Medical Journal
Devram S Ghorpade, Lale Ozcan, Ze Zheng, Sarah M Nicoloro, Yuefei Shen, Emily Chen, Matthias Blüher, Michael P Czech, Ira Tabas
Obesity-induced metabolic disease involves functional integration among several organs via circulating factors, but little is known about crosstalk between liver and visceral adipose tissue (VAT). In obesity, VAT becomes populated with inflammatory adipose tissue macrophages (ATMs). In obese humans, there is a close correlation between adipose tissue inflammation and insulin resistance, and in obese mice, blocking systemic or ATM inflammation improves insulin sensitivity. However, processes that promote pathological adipose tissue inflammation in obesity are incompletely understood...
March 21, 2018: Nature
Karen E Elkind-Hirsch, Martha S Paterson, Donna Shaler, Hanh C Gutowski
OBJECTIVE: Our pilot study examined the effectiveness of sitagliptin-metformin (SITA-MET), metformin (MET), and placebo (P) therapy on fasting and post-glucose challenge glucose levels in postpartum women with prior gestational diabetes mellitus (GDM) and impaired glucose regulation. METHODS: Prediabetic women (N = 36, age 18 to 42 years) with recent GDM were randomized to P (one pill twice a day), MET (1,000 mg twice a day), or SITA-MET (50 mg SITA, 1,000 mg MET twice a day) for 16 weeks in a single-blind fashion...
March 21, 2018: Endocrine Practice
Dandan Zhao, Shaoqian Zhao, Xiao Wang, Mingbo Su, Wen Liu, Qinyun Ma, Jie Hong, Weiqiong Gu, Jingya Li, Ruixin Liu, Guang Ning, Jiqiu Wang, Yifei Zhang
The clinical application of dipeptidyl peptidase IV inhibitors (DPP4i) increasing active glucagon-like peptide-1 (AGLP-1) levels has been linked to pancreatitis, pancreatic tumors, and cardiovascular events. However, DPP4 mutations in humans or the long-term outcomes of high glucagon-like peptide-1 (GLP-1) level exposure have not been reported. A trio family with a proband showing an extremely high AGLP-1 level [defined here as hyperglipemia (hyper-glucagon-like peptide-1-emia)] were conducted whole-exome sequencing for potential pathogenic genetic defects...
2018: Frontiers in Endocrinology
Keiichi Torimoto, Yosuke Okada, Yoshiya Tanaka
Vascular endothelial function is important for maintaining the homeostasis of the living body. Especially, nitric oxide (NO) produced in vascular endothelial cells regulates blood vessel tone and has an antiatherosclerotic effect. Type 2 diabetes is a typical disease that causes impaired vascular endothelial function, resulting in various vascular complications and damage to organs. Cardiovascular disease associated with type 2 diabetes is a chronic inflammatory disease that starts with endothelial dysfunction (ED), and vascular ED is important as an initial change in arteriosclerotic lesions...
2018: Journal of UOEH
Akira Kurozumi, Yosuke Okada, Kei Sugai, Keiichi Torimoto, Yoshiya Tanaka
Our purpose was to determine the effects of teneligliptin and sitagliptin, two dipeptidyl peptidase 4 inhibitors (DPP4-Is) with different half-lives, on glycemic variability and glucagon-like peptide-1 (GLP-1) levels in Japanese patients with type 2 diabetes mellitus (T2DM). The study subjects were 14 drug-naïve patients with T2DM who were allocated to either a 20 mg/day teneligliptin group (n = 7) or a 50 mg/day sitagliptin group (n = 7) for 7 days, then switched to the other treatment for another 7 days...
2018: Journal of UOEH
Connor M Pettem, Jennifer M Briens, David M Janz, Lynn P Weber
Selenium (Se) is considered an essential trace element, involved in important physiological and metabolic functions for all vertebrate species. Fish require dietary concentrations of 0.1-0.5 μg Se/g dry mass (d.m.) to maintain normal physiological and selenoprotein function, however concentrations exceeding 3 μg/g d.m. have been shown to cause toxicity. As Se is reported to have a narrow margin between essentiality and toxicity, there is growing concern surrounding the adverse effects of elevated Se exposure caused by anthropogenic activities...
March 8, 2018: Aquatic Toxicology
Gian Paolo Fadini, Mayur Sarangdhar, Angelo Avogaro
INTRODUCTION: In the SAVOR-TIMI trial, the risk of heart failure (HF) was increased by 27% in T2D patients randomized to the dipeptidyl peptidase-4 inhibitor (DPP4i) saxagliptin. Other studies have provided inconsistent results regarding this association. Herein, we performed a pharmacovigilance analysis of the rate of HF associated with DPP4is, focusing on stimulated reporting and moderation by drug-drug interactions. METHODS: We mined the FDA adverse event (AE) reporting system (FAERS) from 2004q1 to 2017q3, including a total of 9906,642 AE reports...
March 16, 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
Anita D Misra-Hebert, Kevin M Pantalone, Xinge Ji, Alex Milinovich, Tanujit Dey, Kevin M Chagin, Janine M Bauman, Michael W Kattan, Robert S Zimmerman
OBJECTIVE: To identify severe hypoglycemia events, defined as emergency department visits or hospitalizations for hypoglycemia, in patients with type 2 diabetes receiving care in a large health system and to identify patient characteristics associated with severe hypoglycemia events. RESEARCH DESIGN AND METHODS: This was a retrospective cohort study from January 2006 to December 2015 using the electronic medical record in the Cleveland Clinic Health System (CCHS)...
March 16, 2018: Diabetes Care
Soo Lim, Robert H Eckel, Kwang Kon Koh
The final goal in the management of patients with type 2 diabetes (T2D) is reduction in cardiovascular (CV) complications and total mortality. Various factors including hyperglycemia contribute to these complications and mortality directly and indirectly. In recent years, large-scale CV outcome trials with new antidiabetic medications, such as dipeptidyl peptidase-4 (DPP4) inhibitors, glucagon-like peptide-1 (GLP1) receptor agonists, and sodium glucose cotransporter-2 (SGLT2) inhibitors, have been completed...
March 8, 2018: Atherosclerosis
Kana Ide, Masaya Koshizaka, Hirotake Tokuyama, Takahiko Tokuyama, Takahiro Ishikawa, Yoshiro Maezawa, Minoru Takemoto, Koutaro Yokote
BACKGROUND: Patients with type 2 diabetes are at high risk for cardiovascular disease. Although hydroxymethylglutaryl-CoA reductase inhibitors (statins) can reduce cardiovascular events, residual risk remains even after target low-density lipoprotein cholesterol (LDL-C) levels have been achieved. Lipoprotein particle size and fraction changes are thought to contribute to such risks. The purpose of this study was to evaluate the effects of n-3 polyunsaturated fatty acids (n-3 PUFAs), predominantly eicosapentaenoic acid and docosahexaenoic acid, on lipoprotein particle size, concentration, and glycemic control in Japanese patients with type 2 diabetes and hypertriglyceridemia...
March 15, 2018: Lipids in Health and Disease
Weinan Guo, Jinyuan Ma, Tianli Pei, Tao Zhao, Sen Guo, Xiuli Yi, Yu Liu, Shiyu Wang, Guannan Zhu, Zhe Jian, Tianwen Gao, Chunying Li, Wenjun Liao, Qiong Shi
Melanoma is the most malignant skin cancer with increasing incidence worldwide. Although innovative therapies such as BRAF inhibitor and immune checkpoint inhibitor have gained remarkable advances, metastatic melanoma remains an incurable disease for its notorious aggressiveness. Therefore, further clarification of the underlying mechanism of melanoma pathogenesis is critical for the improvement of melanoma therapy. Ubiquitination is an important regulatory event for cancer hallmarks and melanoma development, and the deubiquitinating enzymes including ubiquitin-specific peptidase (USP) families are greatly implicated in modulating cancer biology...
March 14, 2018: Journal of Cellular and Molecular Medicine
Kazuaki Negishi
We are now entering the very exciting era of treatment and management of diabetes mellitus (DM) with the emergence of new therapeutic agents, including sodium-glucose cotransporter 2 inhibitors (SGLT2i) and dipeptidyl peptidase-4 inhibitor (DPP-4i). From a cardiology and echocardiography perspective, the existence of diabetic cardiomyopathy has been proven through over four decades of discussion. DM is highly prevalent in patients with heart failure (HF). Independent associations are found after adjusting for hypertension (HTN) and coronary artery disease (CAD)...
February 2018: Cardiovascular Diagnosis and Therapy
Chen Zou, Changjing Han, Minjie Zhao, Jingjing Yu, Lin Bai, Yuan Yao, Shuaixin Gao, Hui Cao, Zhi Zheng
Background: Preoperative treatment of anti-vascular endothelial growth factor (VEGF) agents is extensively used in proliferative diabetic retinopathy (PDR), but the molecular mechanism is not fully understood. The objective of this research is to observe change of protein profile induced by ranibizumab (an anti-VEGF agent) in vitreous humor from PDR patients and reveal the effects of anti-VEGF treatment on PDR. Methods: A proteomic method was used to identify differentially expressed proteins in vitreous humor...
2018: Clinical Proteomics
Rajesh B Patil, Euzebio G Barbosa, Jaiprakash N Sangshetti, Vishal P Zambre, Sanjay D Sawant
Dipeptidyl peptidase-IV (DPP-IV) inhibitors are promising antidiabetic agents. Currently, several DPP-IV inhibitors have been approved for therapeutic use in diabetes mellitus. Receptor-dependent 4D-QSAR is comparatively a new approach which uses molecular dynamics simulations to generate conformational ensemble profiles of compounds representing a dynamic state of compounds at a target's binding site. This work describes a receptor-dependent 4D-QSAR study on triazolopiperazine derivatives. QSARINS multiple linear regression method was adopted to generate 4D-QSAR models...
March 13, 2018: Molecular Diversity
Se Hee Min, Jeong-Hwa Yoon, Sun Joon Moon, Seokyung Hahn, Young Min Cho
Sodium glucose cotransporter 2 (SGLT2) inhibitors and dipeptidyl peptidase-4 (DPP4) inhibitors have complementary mode of action. For the meta-analysis comparing the efficacy and safety between SGLT2 inhibitor plus DPP4 inhibitor (SGLT2i/DPP4i) and placebo plus DPP4 inhibitor (PCB/DPP4i) in patients with type 2 diabetes mellitus (T2DM), we selected randomized controlled trials from electronic databases by predefined criteria. The primary outcome of interest was the change in glycated hemoglobin A1c (HbA1c) from baseline...
March 13, 2018: Scientific Reports
Milton Packer
Three classes of anti-hyperglycaemic medications are distinguished by their urinary sodium excretion-enhancing and blood pressure-lowering actions: long-acting glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors and sodium-glucose co-transporter-2 inhibitors. Yet, these drugs exert different effects on macrovascular risk. Glucagon-like peptide-1 receptor agonists reduce atherosclerotic thromboembolic events, but have little effect on heart failure; sodium-glucose co-transporter-2 inhibitors decrease the occurrence of heart failure, but have minimal effect on myocardial infarction and stroke; and dipeptidyl peptidase-4 inhibitors do not ameliorate either atherosclerotic thromboembolic events or heart failure...
March 12, 2018: Diabetic Medicine: a Journal of the British Diabetic Association
Chien-Liang Liu, Po-Sheng Yang, Ming-Nan Chien, Yuan-Ching Chang, Chi-Hsin Lin, Shih-Ping Cheng
SPINT1, also known as HAI-1, is a Kunitz-type serine protease inhibitor that inhibits multiple proteases including hepatocyte growth factor (HGF) activator and matriptase. SPINT1 has been shown to modulate HGF/MET activation in certain cancer types. In the present study, we analyzed microarray datasets and found that SPINT1 was consistently upregulated in differentiated thyroid cancer. SPINT1 protein expression was investigated using tissue microarrays and independent samples of our 143 patients. Strong SPINT1 expression was observed in 61-68% of papillary thyroid cancer and 41-50% of follicular thyroid cancer...
March 12, 2018: Histochemistry and Cell Biology
Rattiyaporn Kanlaya, Visith Thongboonkerd
TGF-β1 is a key fibrotic factor mediating epithelial mesenchymal transition (EMT) of epithelial cells through various signaling pathways. However, roles of proteolytic cleavage and endogenous peptide dynamics in TGF-β1-induced EMT remain unknown. We therefore performed quantitative peptidomics of TGF-β1-induced EMT in renal tubular epithelial cells. The acquired mesenchymal characteristics were confirmed, including morphological change (from cobblestone-like to fibroblast-like), decreased epithelial marker (ZO-1), and increased mesenchymal marker (vimentin)...
December 2018: Cell Death Discovery
Yeon Young Cho, Sung-Il Cho
AIMS: We explored the risks associated with metformin plus sulfonylurea (MET+SU) or MET plus a dipeptidyl peptidase-4 inhibitor (MET+DPP4i) for hypoglycemia, cardiovascular disease (CVD) events and all-cause mortality in type 2 diabetes (T2D) patients with comorbidities. METHODS: This retrospective cohort study is based on the South Korean National Health Insurance Service-National Sample Cohort, enrolling T2D patients with one or more diabetes-related comorbidities who switched from monotherapy to MET+SU or MET+DPP4i between July 1, 2008 and December 31, 2013...
March 9, 2018: Metabolism: Clinical and Experimental
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