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Type 3 secretion

Hyun Lee, Minoru Fujimoto, Tomoharu Ohkawara, Hiromi Honda, Satoshi Serada, Yoshio Terada, Tetsuji Naka
Recent evidence suggests that renal tubular injury plays a key role in deterioration of renal function in both chronic kidney disease (CKD) and acute kidney injury (AKI). Since commonly used biochemical indicators such as GFR, serum creatinine, blood urea nitrogen and creatinine clearance are inappropriate for detecting alteration in renal tubules, biomarkers reflecting renal tubular injury have been extensively explored. Our research group identified leucine rich α-2 glycoprotein (LRG) as a novel serum biomarker for various inflammatory diseases such as rheumatoid arthritis and inflammatory bowel disease...
March 16, 2018: Biochemical and Biophysical Research Communications
Doreen Baumann, Helen Salia, Lilo Greune, Stephanie Norkowski, Britta Körner, Zina M Uckeley, Gad Frankel, Marianne Guenot, Christian Rüter, M Alexander Schmidt
Enteropathogenic Escherichia coli (EPEC) subvert host cell signaling pathways by injecting effector proteins via a Type 3 Secretion System (T3SS). The T3SS-dependent EspB protein is a multi-functional effector protein, which contributes to adherence and translocator pore formation and after injection exhibits several intracellular activities. In addition, EspB is also secreted into the environment. Effects of secreted EspB have not been reported thus far. As a surrogate for secreted EspB we employed recombinant EspB (rEspB) derived from the prototype EPEC strain E2348/69 and investigated the interactions of the purified protein with different human epithelial and immune cells including monocytic THP-1 cells, macrophages, dendritic cells, U-937, epithelial T84, Caco-2, and HeLa cells...
March 12, 2018: International Journal of Medical Microbiology: IJMM
Vishal Musale, Yasser H A Abdel-Wahab, Peter R Flatt, J Michael Conlon, Maria Luisa Mangoni
Long-standing Type 2 diabetes is associated with loss of both β-cell function and β-cell mass. Peptides derived from the frog-skin host-defense peptide esculentin-1 have been shown to exhibit potent, broad-spectrum antimicrobial activity. The aim of the present study is to determine whether such peptides also show insulinotropic and β-cell protective activities. Esculentin-1a(1-21).NH2 , esculentin-1b(1-18).NH2 , and esculentin-1a(1-14).NH2 produced concentration-dependent stimulations of insulin release from BRIN-BD11 rat clonal β-cells, 1...
March 17, 2018: Amino Acids
Dafna Greitzer-Antes, Li Xie, Tairan Qin, Huanli Xie, Dan Zhu, Subhankar Dolai, Tao Liang, Fei Kang, Alexandre B Hardy, Yan He, Youhou Kang, Herbert Y Gaisano
The voltage-dependent K+ (Kv) channel Kv2.1 is a major delayed rectifier in many secretory cells, including pancreatic β-cells. In addition, Kv2.1 has a direct role in exocytosis at an undefined step, involving SNARE proteins and independent of its ion-conducting pore function. Here, we elucidated the precise step in exocytosis. We previously reported that syntaxin 3 (Syn-3) is the key syntaxin that mediates exocytosis of newcomer secretory granules that spend minimal residence time on the plasma membrane before fusion...
March 16, 2018: Journal of Biological Chemistry
Geoffrey P Roberts, Richard G Kay, James Howard, Richard H Hardwick, Frank Reimann, Fiona M Gribble
BACKGROUND: Altered enteroendocrine hormone responses are widely believed to underlie the beneficial effects of bariatric surgery in type 2 diabetes. While elevated postprandial glucagon-like peptide-1 (GLP-1) is considered one of the mediators, increased postprandial glucagon levels have recently been implicated. OBJECTIVES: We investigated hormonal responses in lean patients after prophylactic total gastrectomy (PTG), as a model of Roux-en-Y gastric bypass without the confounding effects of obesity or massive weight loss...
February 3, 2018: Surgery for Obesity and related Diseases: Official Journal of the American Society for Bariatric Surgery
Clémence Granier, Alain Gey, Charles Dariane, Arnaud Mejean, Marc-Olivier Timsit, Charlotte Blanc, Virginie Verkarre, Camélia Radulescu, Elisabeth Fabre, Yann Vano, Stéphane Oudard, Cécile Badoual, Éric Tartour
T cells harboring multiple co-inhibitory molecules lose their anti-tumoral functionality. PD-1 is a clinically approved target in cancer therapy, but its expression alone does not mean dysfunctionality. The expression of Tim-3 on numerous cell types (T cell, Treg, dendritic cell, myeloid cells) favors tumor escape to immune cells. Within many tumors, PD-1/Tim-3 coexpressing CD8-T cells lose their ability to secrete cytokines (IFNγ, IL-2, TNFα) and their intratumoral infiltration correlates with a bad prognosis...
March 2018: Médecine Sciences: M/S
Ye Seul Yang, Min Hyuk Lim, Seong Ok Lee, Eun Roh, Chang Ho Ahn, Soo Heon Kwak, Young Min Cho, Sungwan Kim, Andrea Mari, Kyong Soo Park, Hye Seung Jung
AIMS: Angiotensin receptor blockers (ARB) are anti-hypertensive drugs with renal protective effect. Additionally, they have been associated with the delayed onset of type 2 diabetes in high-risk populations, and some ARB were reported to increase insulin secretion and sensitivity in patients with prediabetes. Therefore, we studied the effects of ARB on insulin secretion in hypertensive patients with type 2 diabetes. MATERIALS AND METHODS: Forty-one patients were enrolled in this open-labeled, active comparator-controlled and crossover study...
March 15, 2018: Diabetes, Obesity & Metabolism
Zia Uddin, Yeong Hun Song, Mahboob Ullah, Zuopeng Li, Jeong Yoon Kim, Ki Hun Park
Diabetes mellitus is one of a major worldwide concerns, regulated by either defects in secretion or action of insulin, or both. Insulin signaling down-regulation has been related with over activity of protein tyrosine phosphatase 1B (PTP1B) enzyme, which has been a promising target for the treatment of diabetes mellitus. Herein, activity guided separation of methanol extract (95%) of Dodonaea viscosa aerial parts afforded nine ( 1 - 9 ) polyphenolic compounds, all of them were identified through spectroscopic data including 2D NMR and HREIMS...
2018: Frontiers in Chemistry
Anthony J Kee, Jayshan Chagan, Jeng Yie Chan, Nicole S Bryce, Christine A Lucas, Jun Zeng, Jeff Hook, Herbert Treutlein, D Ross Laybutt, Justine R Stehn, Peter W Gunning, Edna C Hardeman
The development of novel small molecule inhibitors of the cancer-associated tropomyosin 3.1 (Tpm3.1) provides the ability to examine the metabolic function of specific actin filament populations. We have determined the ability of these anti-Tpm (ATM) compounds to regulate glucose metabolism in mice. Acute treatment (1 h) of wild-type (WT) mice with the compounds (TR100 and ATM1001) led to a decrease in glucose clearance due mainly to suppression of glucose-stimulated insulin secretion (GSIS) from the pancreatic islets...
March 15, 2018: Scientific Reports
Sudha S Shankar, R Ravi Shankar, Lori A Mixson, Deborah L Miller, Barnali Pramanik, Amy K O'Dowd, Donna M Williams, Clay B Frederick, Chan R Beals, S Aubrey Stoch, Helmut O Steinberg, David E Kelley
Oxyntomodulin (OXM), an enteroendocrine hormone, causes appetite suppression, increased energy expenditure, and weight loss in obese humans via activation of GLP-1 and glucagon receptors. However, the effects of OXM on glucose homeostasis remain ill-defined. To address this gap, we evaluated the effects of an intravenous (IV) infusion of native OXM on insulin secretory rates (ISR) and glycemic excursion in a graded glucose infusion (GGI) procedure in two separate randomized, placebo-controlled, single dose crossover trials in 12 overweight and obese subjects without diabetes, and in 12 obese subjects with Type 2 diabetes (T2DM) respectively, using the GLP-1 analog, liraglutide as a comparator in the T2DM...
March 15, 2018: Diabetes
Brendan M Everett, Marc Y Donath, Aruna D Pradhan, Tom Thuren, Prem Pais, Jose C Nicolau, Robert J Glynn, Peter Libby, Paul M Ridker
BACKGROUND: Subclinical inflammation mediated in part by interleukin-1 beta (IL-1β) participates in peripheral insulin resistance and impaired pancreatic insulin secretion. OBJECTIVES: We tested the hypothesis that canakinumab, an IL-1β inhibitor, reduces incident diabetes. METHODS: The Canakinumab Antiinflammatory Thrombosis Outcomes Study (CANTOS) randomized 10,061 patients with prior MI and high-sensitivity C-reactive protein (hsCRP) ≥2 mg/L to placebo or canakinumab at doses of 50mg, 150mg, or 300mg subcutaneously once every three months...
March 3, 2018: Journal of the American College of Cardiology
Phu Hai Nguyen, Erika I Lutter, Ted Hackstadt
Chlamydia trachomatis is an obligate intracellular bacterium that replicates within a vacuole termed an inclusion. At the end of their intracellular developmental cycle, chlamydiae are released either by lysis of the host cell or extrusion of the intact inclusion. The inclusion membrane is extensively modified by the insertion of type III secreted inclusion membrane proteins, Incs, which contribute to inclusion membrane structure and facilitate host-pathogen interactions. An interaction was identified between the inclusion membrane protein, MrcA, and the Ca2+ channel inositol-1,4,5-trisphosphate receptor, type 3 (ITPR3)...
March 2018: PLoS Pathogens
Tomoko Kubori, Tomoe Kitao, Hiroki Ando, Hiroki Nagai
The intracellular bacterial pathogen Legionella pneumophila establishes the replicative niche as a result of the actions of a large array of effector proteins delivered via the Legionella type IV secretion system (T4SS). Many effector proteins are expected to be involved in biogenesis and regulation of the Legionella-containing vacuole (LCV) that is highly decorated with ubiquitin. Here, we identified a Legionella deubiquitinase (DUB), designated LotA, by carrying out a genome analysis to find proteins resembling the eukaryotic ovarian tumor (OTU) superfamily of cysteine proteases...
March 15, 2018: Cellular Microbiology
Valeryi K Lishko, Valentin P Yakubenko, Tatiana P Ugarova, Nataly P Podolnikova
Platelet Factor 4 (PF4) is one of the most abundant cationic proteins secreted from α-granules of activated platelets. Based on its structure, PF4 was assigned to the CXC family of chemokines and has been shown to have numerous effects on myeloid leukocytes. However, the receptor for PF4 remains unknown. Here, we demonstrate that PF4 induces leukocyte responses through the integrin Mac-1 (αM β2 , CD11b/CD18). Human neutrophils, monocytes, U937 monocytic and HEK293 cells expressing Mac-1 strongly adhered to immobilized PF4 in a concentration-dependent manner...
March 14, 2018: Journal of Biological Chemistry
Habtamu Wondifraw Baynes, Seifu Mideksa, Sintayehu Ambachew
Polyunsaturated Fatty acids have multiple effects in peripheral tissues and pancreatic beta cell function. The n-3 Polyunsaturated Fatty acids prevent and reverse high-fat-diet induced adipose tissue inflammation and insulin resistance. Insulin secretion is stimulated by glucose, amino acids, and glucagon- like peptide-1 in tissue containing high levels of n-3 Polyunsaturated Fatty acids than lower level of n-3 Polyunsaturated Fatty acids. Also, n-3 Polyunsaturated Fatty acids led to decreased production of prostaglandin, which in turn contributed to the elevation of insulin secretion...
March 14, 2018: Adipocyte
Xin Qian, Hui Wang, Gangyi Yang, Zhengnan Gao, Yong Luo, Aimei Dong, Fang Zhang, Mingtong Xu, Shiping Liu, Xin Yang, Yanyan Chen, Guangwei Li
INTRODUCTION: To investigate the effects of pioglitazone (PIO) on insulin resistance and first phase insulin secretion among obese and lean Chinese people with type 2 diabetes mellitus (T2DM). METHODS: Sixty-eight drug-naïve patients with T2DM were treated with PIO for 16 weeks. Before and after the treatment, insulin sensitivity was evaluated by the euglycemic hyperinsulinemic clamp test. Plasma insulin levels at 0, 3, 5, 7, and 10 min during intravenous glucose tolerance test were determined to calculate the first phase insulin secretion and pancreatic β-cell function...
March 13, 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
Roberta Lotti, En Shu, Tiziana Petrachi, Alessandra Marconi, Elisabetta Palazzo, Marika Quadri, Ann Lin, Lorraine A O'Reilly, Carlo Pincelli
Pemphigus is a blistering disease characterized by pemphigus autoantibodies (PVIgG) directed mostly against desmogleins (Dsgs), resulting in the loss of keratinocyte adhesion (acantholysis). Yet, the mechanisms underlying blister formation remain to be clarified. We have shown previously that anti-Fas ligand (FasL) antibody (Ab) prevents PVIgG-induced caspase-8 activation and Dsg cleavage in human keratinocytes, and that sera from pemphigus patients contain abnormally increased levels of FasL. Here, we demonstrate that recombinant FasL induces the activation of caspases prior to Dsg degradation, and anti-FasL Ab prevents acantholysis in cultured keratinocytes...
2018: Frontiers in Immunology
Nejla Sellami, Laila Ben Lamine, Amira Turki, Sameh Sarray, Mohammed Jailani, Abrar K Al-Ansari, Mohamed Ghorbel, Touhami Mahjoub, Wassim Y Almawi
BACKGROUND: Vascular endothelial growth factor (VEGF) contributes to type 2 diabetes (T2DM) pathogenesis, and genetic variations in VEGFA gene were suggested to influence VEGF secretion and T2DM pathogenesis. AIM: To evaluate the association of specific VEGFA variants with altered VEGF levels, and with T2DM among Tunisians. SUBJECTS AND METHODS: A retrospective case-control study, performed on 815 T2DM patients, and 805 healthy controls. VEGF levels were measured by ELISA, genotyping of VEGFA variants was done by allelic exclusion method (real-time PCR)...
March 10, 2018: Cytokine
Onalenna Kereilwe, Kiran Pandey, Vitaliano Borromeo, Hiroya Kadokawa
Preantral and small antral follicles may secret anti-Müllerian hormone (AMH) to control gonadotrophin secretion from ruminant gonadotrophs. The present study investigated whether the main receptor for AMH, AMH receptor type 2 (AMHR2), is expressed in gonadotrophs of postpubertal heifers to control gonadotrophin secretion. Expression of AMHR2 mRNA was detected in anterior pituitaries (APs) of postpubertal heifers using reverse transcription-polymerase chain reaction. An anti-AMHR2 chicken antibody was developed against the extracellular region near the N-terminus of bovine AMHR2...
March 14, 2018: Reproduction, Fertility, and Development
Ya-Kun Li, Dong-Xia Ma, Zhi-Min Wang, Xiao-Fan Hu, Shang-Lin Li, Hong-Zhe Tian, Meng-Jun Wang, Yan-Wen Shu, Jun Yang
Renal fibrosis is recognized as the common route of all chronic kidney disease (CKD) progressing to end-stage renal disease (ESRD). Additionally, accumulating evidence suggests that epithelial-mesenchymal transition (EMT) plays a significant role in the process of renal fibrogenesis. Liraglutide is a long-acting glucagon-like peptide-1 (GLP-1) analog that has been widely used to treat type 2 diabetes. Recent studies have demonstrated that the GLP-1 analogs could also exert protective effects in cardiac fibrosis models...
March 9, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
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