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Piotr Kocełak, Aleksander Owczarek, Maria Bożentowicz-Wikarek, Aniceta Brzozowska, Małgorzata Mossakowska, Tomasz Grodzicki, Andrzej Więcek, Jerzy Chudek, Magdalena Olszanecka-Glinianowicz
PURPOSE: The aim of the study was to assess plasma RBP4 concentration in elderly subjects in relation to nutritional status and kidney function in the population of the PolSenior Study. MATERIAL AND METHODS: We assessed RBP4, glucose, insulin, albumin, lipid profile, C-reactive protein, (hsCRP) and creatinine concentrations in 2614 PolSenior Study participants (1235 women and 1379 men). The study group was divided based on BMI and HOMA-IR values, and the occurrence of diabetes...
July 16, 2018: Advances in Medical Sciences
S Roat-Shumway, T E Wroolie, K Watson, A F Schatzberg, N L Rasgon
BACKGROUND: Previous studies have shown that individuals with mood disorders have a higher prevalence of both hypercortisolemia and insulin resistance. Insulin resistance is posited to contribute to the cognitive deficits observed in individuals who have depression. However, the mechanistic relationship between cortisol and insulin within the central nervous system remains to be further elucidated. This study aimed to evaluate the effects of the antiglucocorticoid agent, mifepristone, on metabolic function and cognitive performance in individuals receiving treatment for depressive disorders who were euthymic at baseline...
July 10, 2018: Journal of Affective Disorders
Laurie K Bale, Sally A West, Cheryl A Conover
Although implicated in cardiovascular disease, little is known about the fat surrounding the heart. In humans, epicardial fat is the visceral fat depot of the heart, which directly contacts the myocardium. This strategically placed fat depot is thought to produce bioactive molecules that could affect cardiac function. A major limitation in understanding the biology of epicardial fat is its restricted access in humans and its seeming absence in commonly-used experimental animal models. Although laboratory mice do not have epicardial fat per se, they do have a fat depot around the heart...
July 11, 2018: Growth Hormone & IGF Research
Xinyi Tan, Xiaolin Liu, Yan Zhang, Hongjuan Zhang, Xiaoyang Lin, Chenguang Pu, Jingxin Gou, Haibing He, Tian Yin, Yu Zhang, Xing Tang
When intravenous or subcutaneous administration of insulin, various side effects or possible risks have been reported. Oral administration of insulin has significant advantages of convenience, painless and mimetic endogenous insulin pathway, and thus it presents patients compliance, protects pancreatic β-cells and lessens adverse effects caused by long-term injection. This challenging oral delivery of insulin can be achieved by promising silica nanoparticles (SNs), especially mesoporous silica nanoparticles (MSNs), with controllable morphology and high loading efficiency...
July 19, 2018: Expert Opinion on Drug Delivery
Yang Lee, Sanjukta Chakraborty, Cynthia J Meininger, Mariappan Muthuchamy
OBJECTIVE: Lymphatic vessel dysfunction and increased lymph leakage have been directly associated with several metabolic diseases. However, the underlying cellular mechanisms causing lymphatic dysfunction have not been determined. Aberrant insulin signaling affects the metabolic function of cells, and consequently impairs tissue function. We hypothesized that insulin resistance in lymphatic endothelial cells (LECs) decreases eNOS activity, disrupts barrier integrity increases permeability, and activates mitochondrial dysfunction and pro-inflammatory signaling pathways...
July 19, 2018: Microcirculation: the Official Journal of the Microcirculatory Society, Inc
Junwon Lee, Sang-Hwi Choi, Young-Beom Kim, Ikhyun Jun, Jin Jea Sung, Dongjin R Lee, Yang In Kim, Myung Soo Cho, Suk Ho Byeon, Dae-Sung Kim, Dong-Wook Kim
Purpose: We aimed to establish an efficient method for retinal ganglion cell (RGC) differentiation from human pluripotent stem cells (hPSCs) using defined factors. Methods: To define the contribution of specific signal pathways to RGC development and optimize the differentiation of hPSCs toward RGCs, we examined RGC differentiation in three stages: (1) eye field progenitors expressing the eye field transcription factors (EFTFs), (2) RGC progenitors expressing MATH5, and (3) RGCs expressing BRN3B and ISLET1...
July 2, 2018: Investigative Ophthalmology & Visual Science
Ju-Fang Teng, Chien-Hsing Lee, Tai-Hao Hsu, Hui-Chen Lo
Polysaccharides derived from mushrooms have potential to control blood sugar, reduce insulin resistance and prevent diabetic complications. The intracellular polysaccharopeptides of Trametes versicolor (TV) have been used as immunologic and oncologic adjuvants. The aim of this study was to investigate the potential activities and mechanisms of extracellular polysaccharopeptides (ePSP) obtained from TV strain LH-1 on regulating glucose homeostasis. Human hepatoma HepG2 cells incubated with normal glucose (5...
2018: PloS One
Sona Margaryan, Agata Witkowicz, Arsen Arakelyan, Anna Partyka, Lidia Karabon, Gayane Manukyan
Fas/Fas ligand system was shown to be related to insulin resistance and type 2 diabetes mellitus (T2DM). However, the role of soluble Fas ligand (sFasL) in functioning of immune cells in type 2 diabetes mellitus (T2DM) has not been studied yet. The aim of the present study was to determine in vitro effects of sFasL on neutrophil activation and apoptosis. We demonstrate here that sFasL exhibited proinflammatory effect and induced mRNA levels of caspase-1, NF-κB, IL-1β and CD18 expression. At the same time, sFasL induced reactive oxygen species (ROS) production...
2018: PloS One
Hossein Sendi, Ivy Mead, Meimei Wan, Marjan Mehrab-Mohseni, Kenneth Koch, Anthony Atala, Herbert L Bonkovsky, Colin E Bishop
To investigate the role of miR-122 in the development and regression of non-alcoholic fatty liver disease (NAFLD) in vitro, we used multicellular 3D human liver organoids developed in our laboratory. These organoids consist of primary human hepatocytes, Kupffer cells, quiescent stellate cells and liver sinusoidal endothelial cells. They remain viable and functional for 4 weeks expressing typical markers of liver function such as synthesis of albumin, urea, and alpha-1 p450 drug metabolism. Before mixing, hepatic cells were transduced with lentivirus to inhibit miR122 expression (ABM, CA)...
2018: PloS One
Jack Williams, Nicholas Jacus, Kevin Kavalackal, Kirstie K Danielson, Rebecca S Monson, Yong Wang, Jose Oberholzer
Islet cell transplantation is a promising functional cure for type 1 diabetes; however, maintaining long-term islet graft function and insulin independence is difficult to achieve. In this short report we present a patient with situs inversus, who at the time of islet transplantation had a 26-year history of type 1 diabetes, complicated by hypoglycemic unawareness and severe hypoglycemic events. After a single allogeneic islet transplant of a low islet mass, and despite developing de novo anti-insulin and anti-GAD65 autoantibodies, the patient has remarkably maintained insulin independence with tight glycemic control and normal metabolic profiles for 10 years, after receiving prolonged non-T-cell depleting immunosuppression...
July 19, 2018: Islets
Perry A Zirkel
This article summarizes the facts and rulings of a recent, representative federal court decision concerning the legal claims of a school nurse who had engaged in advocacy for student safety, with particular attention to a student with insulin-dependent diabetes who committed suicide. The discussion of the court's rulings for the school nurse's various legal claims identifies the difference between ethical interpretation in terms of prevailing perceptions among school nurses and legal protection in terms of the current state of the case law specific to such advocacy...
July 1, 2018: NASN School Nurse
S Alfieri, A Agnes, F Rosa, D Di Miceli, D L Grieco, F Scaldaferri, A Gasbarrini, G B Doglietto, G Quero
OBJECTIVE: Even if pancreatic pathologies, residual fibrosis, residual amount of parenchyma, and anastomotic patency are recognized as main causes of exocrine and glycemic impairment after pancreaticoduodenectomy (PD), few data are reported concerning the role of the different pancreatic remnant treatment techniques. The objective of the study is to assess and compare exocrine functionality, glycemic pattern, nutritional status, and quality of life (QoL) after PD between pancreaticojejunostomy (PJ) and pancreatic duct occlusion (PDO), both in an objective and a subjective manner...
July 2018: European Review for Medical and Pharmacological Sciences
Jing Su, Yan Li, Guanglong Su, Jing Wang, Ting Qiu, Rong Ma, Lei Zhao
The autoimmune and gene etiology are implicated in the pathogenesis of polycystic ovary syndrome (PCOS). The cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) is important for negative regulation of T-cell activation, and CTLA4 gene has been identified as a risk factor for some autoimmune diseases. However, none studies have been performed about the association between PCOS and the CTLA4 gene before. Here, we aimed to investigate the association of CTLA4 with PCOS in the Chinese Han population though a case-control association analysis of 606 individuals...
July 2018: Medicine (Baltimore)
Mostafa Elhelbawy, Wael Abdel-Razek, Ayman Alsebaey, Mohamed Hashim, Hassan Elshenawy, Imam Waked
BACKGROUND: Insulin resistance (IR) is a common complication in chronic hepatitis C virus (HCV) patients. The impact of IR on outcome of therapy with direct antivirals has not been studied. AIM: The aim was to assess the impact of direct-acting antiviral (DAA) therapy on IR status in chronic HCV patients. PATIENTS AND METHODS: A total of 511 patients [mean age: 50.7±10.4 years, 29.7% pegylated interferon and ribavirin (RBV) experienced] were enrolled...
July 18, 2018: European Journal of Gastroenterology & Hepatology
Jiping Sun, Fei Zhao, Wenjing Zhang, Jia Lv, Jing Lv, Aiping Yin
BMSCs are important in replacement therapy of diabetic nephropathy (DN). MiR-124a exerts effect on the differentiation capability of pancreatic progenitor cells. The objective of this study was to explore the molecular mechanisms, the functions of miR-124a and bone marrow mesenchymal stem cells (BMSCs) in the treatment of DN. Characterizations of BMSCs were identified using the inverted microscope and flow cytometer. The differentiations of BMSCs were analysed by immunofluorescence assay and DTZ staining. The expression levels of islet cell-specific transcription factors, apoptosis-related genes, podocytes-related genes and Notch signalling components were detected using quantitative real-time reverse transcription PCR (qRT-PCR) and Western blot assays...
July 19, 2018: Journal of Cellular and Molecular Medicine
Sudarsana Reddy Vanga, Jonas Sävmarker, Leelee Ng, Mats Larhed, Mathias Hallberg, Johan Åqvist, Anders Hallberg, Siew Yeen Chai, Hugo Gutiérrez-de-Terán
The insulin-regulated aminopeptidase (IRAP) is a membrane-bound zinc metallopeptidase with many important regulatory functions. It has been demonstrated that inhibition of IRAP by angiotensin IV (Ang IV) and other peptides, as well as more druglike inhibitors, improves cognition in several rodent models. We recently reported a series of aryl sulfonamides as small-molecule IRAP inhibitors and a promising scaffold for pharmacological intervention. We have now expanded with a number of derivatives, report their stability in liver microsomes, and characterize the activity of the whole series in a new assay performed on recombinant human IRAP...
April 30, 2018: ACS Omega
Sandip Dolui, Anupam Roy, Uttam Pal, Achintya Saha, Nakul C Maiti
Engaging Raman spectroscopy as a primary tool, we investigated the early events of insulin fibrilization and determined the structural content present in oligomer and protofibrils that are formed as intermediates in the fibril formation pathway. Insulin oligomer, as obtained upon incubation of zinc-free insulin at 60 °C, was mostly spherical in shape, with a diameter of 3-5 nm. Longer incubation produced "necklace"-like beaded protofibrillar assembly species. These intermediates eventually transformed into 5-8 nm thick fibers with smooth surface texture...
February 28, 2018: ACS Omega
Karolina Arkell, Martin P Breil, Søren S Frederiksen, Bernt Nilsson
In the many published theories on the retention in reversed-phase chromatography (RPC), the focus is generally on the effect of the concentration of the mobile phase modulator(s), although temperature is known to have a significant influence both on the retention and on the selectivity between the adsorbates. The aim of this study was to investigate and model the combined effects of the temperature and the modulator concentrations on RPC of three insulin variants. KCl and ethanol were used as mobile phase modulators, and the experiments were performed on two different adsorbents, with C18 and C4 ligands...
February 28, 2018: ACS Omega
Patrick L Donabedian, Mallory Evanoff, Florencia A Monge, David G Whitten, Eva Y Chi
Developing new molecular ligands for the direct detection and tracking of amyloid protein aggregates is key to understanding and defeating myriad neurodegenerative and other disorders including Alzheimer's and Parkinson's diseases. A crucial factor in the performance of an amyloid dye is its ability to detect the amyloid structural motif independent of the sequence of the amyloid-forming protomer. The current study investigates structure-function relationships of a class of novel phenyleneethynylene (PPE)-based dyes and fluorescent polymers using amyloid fibrils formed by two model proteins: lysozyme and insulin...
July 31, 2017: ACS Omega
Sudha S Shankar, Douglas S Lee, Ralph H Raymond, Roberto A Calle, Claudio Cobelli, Atalanta Ghosh, R Paul Robertson, Hartmut Ruetten, Myrlene A Staten, Darko Stefanovski, Adrian Vella, Sanya Whitaker, David A Fryburg
Standard practice to minimize variability in beta cell function (BCF) measurement is to test in inpatient (IP) settings. IP testing strains trial subjects, investigators, and budgets. Outpatient (OP) testing may be a solution although there are few reports on OP BCF testing variability. We compared variability metrics between OP and IP from a standardized mixed meal tolerance test (MMTT) and arginine stimulation test (AST) in two separate type 2 diabetes (T2DM) cohorts (OP, n = 20; IP n = 22) in test-retest design...
June 2018: Contemporary Clinical Trials Communications
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