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https://www.readbyqxmd.com/read/29453154/unique-pharmacology-of-a-novel-allosteric-agonist-sensitizer-insulin-receptor-monoclonal-antibody
#1
Simon A Hinke, Anne M Cieniewicz, Thomas Kirchner, Katharine D'Aquino, Rupesh Nanjunda, Jason Aligo, Robert Perkinson, Philip Cooper, Ken Boayke, Mark L Chiu, Steve Jarantow, Eilyn R Lacy, Yin Liang, Dana L Johnson, Jean M Whaley, Russell B Lingham, Anthony J Kihm
OBJECTIVE: Insulin resistance is a key feature of Type 2 Diabetes (T2D), and improving insulin sensitivity is important for disease management. Allosteric modulation of the insulin receptor (IR) with monoclonal antibodies (mAbs) can enhance insulin sensitivity and restore glycemic control in animal models of T2D. METHODS: A novel human mAb, IRAB-A, was identified by phage screening using competition binding and surface plasmon resonance assays with the IR extracellular domain...
February 3, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29453041/microrna-signature-of-regulatory-t-cells-in-health-and-autoimmunity
#2
REVIEW
Mehdi Soltanzadeh-Yamchi, Mehdi Shahbazi, Saeed Aslani, Mousa Mohammadnia-Afrouzi
MicroRNAs (miRNAs) are small RNA molecules with regulatory functions on the expression of genes through binding directly to target messenger RNA (mRNA) transcripts, eventuating in gene expression suppression via translational hindrance and/or target mRNA cleavage. These molecules have been established to participate in numerous critical cellular settings, including differentiation, development, and function of immune cells. As an important suppressor cell of immune system, regulatory T cells (Tregs) are important in modulating the immune homeostasis as well as tolerance to self-antigens...
February 13, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29449530/the-type-2-diabetes-associated-hmg20a-gene-is-mandatory-for-islet-beta-cell-functional-maturity
#3
Jose M Mellado-Gil, Esther Fuente-Martín, Petra I Lorenzo, Nadia Cobo-Vuilleumier, Livia López-Noriega, Alejandro Martín-Montalvo, Irene de Gracia Herrera Gómez, Maria Ceballos-Chávez, Laura Gómez-Jaramillo, Antonio Campos-Caro, Silvana Y Romero-Zerbo, Júlia Rodríguez-Comas, Joan-Marc Servitja, Gemma Rojo-Martinez, Abdelkrim Hmadcha, Bernat Soria, Marco Bugliani, Piero Marchetti, Francisco J Bérmudez-Silva, Jose C Reyes, Manuel Aguilar-Diosdado, Benoit R Gauthier
HMG20A (also known as iBRAF) is a chromatin factor involved in neuronal differentiation and maturation. Recently small nucleotide polymorphisms (SNPs) in the HMG20A gene have been linked to type 2 diabetes mellitus (T2DM) yet neither expression nor function of this T2DM candidate gene in islets is known. Herein we demonstrate that HMG20A is expressed in both human and mouse islets and that levels are decreased in islets of T2DM donors as compared to islets from non-diabetic donors. In vitro studies in mouse and human islets demonstrated that glucose transiently increased HMG20A transcript levels, a result also observed in islets of gestating mice...
February 15, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29447380/sirtuins-in-gamete-biology-and-reproductive-physiology-emerging-roles-and-therapeutic-potential-in-female-and-male-infertility
#4
Carla Tatone, Giovanna Di Emidio, Arcangelo Barbonetti, Gaspare Carta, Alberto M Luciano, Stefano Falone, Fernanda Amicarelli
BACKGROUND: Sirtuins (SIRT1-7) are a family of NAD+-dependent deacetylases that catalyze post-translational modifications of proteins. Together, they respond to metabolic challenges, inflammatory signals or hypoxic/oxidative stress, and are associated with aging and longevity. The role of Sirtuins in the regulation of fertility emerged in 2003 when a defective reproductive phenotype was observed in SIRT1-null mice. Although studies on Sirtuins in reproductive biology have been increasing in the last years, a recent comprehensive update on this issue is still lacking...
February 13, 2018: Human Reproduction Update
https://www.readbyqxmd.com/read/29446740/role-of-immune-cells-in-diabetic-kidney-disease
#5
Xiaoqian Yang, Shan Mou
Diabetic kidney disease (DKD) is one of the major complications of diabetes mellitus (DM) and is currently the most common cause of end-stage renal disease (ESRD) worldwide. Traditionally, DKD is considered a disease which has nothing to do with the immune system, and the pathogenesis is mainly characterized to be metabolic disturbance. Recent growing evidence indicates immunologic and inflammatory mechanisms in the development and progression of DKD. This overview of macrophages, dendritic cells, T lymphocytes, B lymphocytes, neutrophils and mast cells is closely involved in the pathologic process of DKD, with more emphasis on the leucocyte accumulation and related molecular mechanisms...
February 13, 2018: Current Gene Therapy
https://www.readbyqxmd.com/read/29445964/different-methods-for-modelling-severe-hypoglycaemic-events-implications-for-effectiveness-costs-and-health-utilities
#6
Edna Keeney, Dalia Dawoud, Sofia Dias
BACKGROUND: Clinical trials report severe hypoglycaemic events as the number of patients with at least one event out of the total randomised or number of events for a given total exposure. Different network meta-analysis models have been used to analyse these different data types. OBJECTIVE: This aim of this article was to establish the impact of using the different models on effectiveness, costs and health utility estimates. METHODS: We analysed a dataset used in a recent network meta-analysis of severe hypoglycaemic events conducted to inform National Institute for Health and Care Excellence recommendations regarding basal insulin choice for patients with type 1 diabetes mellitus...
February 14, 2018: PharmacoEconomics
https://www.readbyqxmd.com/read/29444822/the-protein-kinase-perk-eif2ak3-regulates-proinsulin-processing-not-via-protein-synthesis-but-by-controlling-endoplasmic-reticulum-chaperones
#7
Carrie R Sowers, Rong Wang, Rebecca A Bourne, Barbara C McGrath, Jingjie Hu, Sarah C Bevilacqua, James C Paton, Adrienne W Paton, Sophie Collardeau-Frachon, Marc Nicolino, Douglas R Cavener
Loss-of-function mutations of the protein kinase PERK (EIF2AK3) in humans and mice cause permanent neonatal diabetes and severe proinsulin aggregation in the endoplasmic reticulum (ER), highlighting the essential role of PERK in insulin production in pancreatic β cells. As PERK is generally known as a translational regulator of the Unfolded Protein Response (UPR), the underlying cause of these β cell defects has often been attributed to derepression of proinsulin synthesis, resulting in proinsulin overload in the ER...
February 14, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29444223/glp-1-receptor-expression-within-the-human-heart
#8
Laurie L Baggio, Bernardo Yusta, Erin E Mulvihill, Xiemin Cao, Catherine J Streutker, Jagdish Butany, Thomas P Cappola, Kenneth B Margulies, Daniel J Drucker
Glucagon-like peptide-1 receptor (GLP-1R) agonists, used to treat type 2 diabetes and obesity, reduce rates of myocardial infarction and cardiovascular death. The GLP-1R has been localized to the human sinoatrial node; however, its expression in ventricular tissue remains uncertain. Here we studied GLP-1R expression in the human heart using GLP-1R-directed antisera, quantitative PCR, reverse transcription PCR to detect full length mRNA transcripts, and in situ hybridization. GLP1R mRNA transcripts, encompassing the entire open reading frame, were detected in all four cardiac chambers from 15 hearts at levels approximating those detected in human pancreas...
February 12, 2018: Endocrinology
https://www.readbyqxmd.com/read/29444133/a-long-term-mechanistic-computational-model-of-physiological-factors-driving-the-onset-of-type-2-diabetes-in-an-individual
#9
Joydeep Sarkar, Gaurav Dwivedi, Qian Chen, Iris E Sheu, Mark Paich, Colleen M Chelini, Paul M D'Alessandro, Samuel P Burns
A computational model of the physiological mechanisms driving an individual's health towards onset of type 2 diabetes (T2D) is described, calibrated and validated using data from the Diabetes Prevention Program (DPP). The objective of this model is to quantify the factors that can be used for prevention of T2D. The model is energy and mass balanced and continuously simulates trajectories of variables including body weight components, fasting plasma glucose, insulin, and glycosylated hemoglobin among others on the time-scale of years...
2018: PloS One
https://www.readbyqxmd.com/read/29432589/changing-change-adaptations-of-an-evidence-based-telehealth-cardiovascular-disease-risk-reduction-intervention
#10
Leah L Zullig, Felicia McCant, Mina Silberberg, Fred Johnson, Bradi B Granger, Hayden B Bosworth
Relatively few successful medication adherence interventions are translated into real-world clinical settings. The Prevention of Cardiovascular Outcomes in African Americans with Diabetes (CHANGE) intervention was originally conceived as a randomized controlled trial to improve cardiovascular disease-related medication adherence and health outcomes. The purpose of the study was to describe the translation of the CHANGE trial into two community-based clinical programs. CHANGE 2 was available to Medicaid patients with diabetes and hypertension whose primary care homes were part of a care management network in the Northern Piedmont region of North Carolina...
February 8, 2018: Translational Behavioral Medicine
https://www.readbyqxmd.com/read/29431147/the-pathogenetic-role-of-%C3%AE-cell-mitochondria-in-type-2-diabetes
#11
REVIEW
Malin Fex, Lisa M Nicholas, Neelanjan Vishnu, Anya Medina, Vladimir V Sharoyko, David G Nicholls, Peter Spégel, Hindrik Mulder
Mitochondrial metabolism is a major determinant of insulin secretion from pancreatic β-cells. Type 2 diabetes evolves when β-cells fail to release appropriate amounts of insulin in response to glucose. This results in hyperglycemia and metabolic dysregulation. Evidence has recently been mounting that mitochondrial dysfunction plays an important role in these processes. Monogenic dysfunction of mitochondria is a rare condition but causes a type 2 diabetes-like syndrome owing to β-cell failure. Here, we describe novel advances in research on mitochondrial dysfunction in the β-cell in type 2 diabetes, with a focus on human studies...
March 2018: Journal of Endocrinology
https://www.readbyqxmd.com/read/29428128/role-of-forkhead-box-o-foxo-transcription-factor-in-aging-and-diseases
#12
REVIEW
Neelam Tia, Alok Kumar Singh, Poorti Pandey, Chandra Shekhar Azad, Pritee Chaudhary, Indrajeet Singh Gambhir
Fork head box O (FOXO) transcription factor is a key player in an evolutionarily conserved pathway. The mammalian FOXO family consists of FOXO1, 3, 4 and 6, are highly similar in their structure, function and regulation. To maintain optimum body function, the organisms have developed complex mechanisms for homeostasis. Importantly, it is well known that when these mechanisms dysregulate it results in the development of age-related disease. FOXO proteins are involved in a diverse cellular function and also have clinical significance including cell cycle arrest, cell differentiation, tumour suppression, DNA repair, longevity, diabetic complications, immunity, wound healing, regulation of metabolism and thus treatment of several types of diseases...
March 30, 2018: Gene
https://www.readbyqxmd.com/read/29424303/antiplatelet-for-coronary-artery-disease-in-specific-condition-no-size-fits-all
#13
Benny M Setiadi, Muhammad Munawar, Beny Hartono, Adhitia B Prakoso, Anggia C Lubis, Reza M Munandar
Antiplatelet is the cornerstone therapy for patient with coronary artery disease. Several comorbidities can influence the efficacy and safety of antiplatelet agent. Diabetes mellitus is characterized by increased platelet reactivity and reduced response to antiplatelet. Elderly patients have both reduced response to antiplatelet and increased risk of bleeding. Patients with renal dysfunction also had decreased efficacy of antiplatelet accompanied with increased risk of bleeding. In patients with atrial fibrillation, the concomitant use of anticoagulant with antiplatelet poses an increased risk of bleeding...
February 8, 2018: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/29424123/mouse-models-of-nonalcoholic-steatohepatitis-a-reflection-on-recent-literature
#14
REVIEW
Fahrettin Haczeyni, Matthew M Yeh, George N Ioannou, Isabelle A Leclercq, Robert Goldin, Yock Young Dan, Jun Yu, Narcissus C Teoh, Geoffrey C Farrell
Nonalcoholic steatohepatitis (NASH) is strongly associated with overnutrition, insulin resistance, and predisposition to type 2 diabetes. To critically analyze the translational significance of currently-used animal models of NASH, we reviewed articles published during the last three years that studied NASH pathogenesis using mouse models. Among 146 articles, 34 (23%) used models in which overnutrition was reported, and 36 (25%) demonstrated insulin resistance, with or without glucose intolerance. Half the articles contained no information on whether mice exhibited overnutrition or insulin resistance...
February 9, 2018: Journal of Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29423188/availability-of-brands-of-six-essential-medicines-in-124-pharmacies-in-maharashtra
#15
Colin Millard, Abhay B Kadam, Rushikesh Mahajan, Allyson M Pollock, Petra Brhlikova
Background: The aim of this study is to assess the availability and rational use of six essential medicines in private retail outlets in Maharashtra state. The study focuses on the range of brands for each medicine, and the availability of these brands in the pharmacies. The medicines were chosen because they are included in the World Health Organization's (WHO) essential medicines list (EML), the Indian national and Maharashtra state medicines list, and are all included in existing Indian public health initiatives and national disease control programmes...
June 2018: Journal of Global Health
https://www.readbyqxmd.com/read/29420964/metabolic-surgery-weight-loss-diabetes-and-beyond
#16
REVIEW
Manan Pareek, Philip R Schauer, Lee M Kaplan, Lawrence A Leiter, Francesco Rubino, Deepak L Bhatt
The alarming rise in the worldwide prevalence of obesity is paralleled by an increasing burden of type 2 diabetes mellitus. Metabolic surgery is the most effective means of obtaining substantial and durable weight loss in individuals with obesity. Randomized trials have recently shown the superiority of surgery over medical treatment alone in achieving improved glycemic control, as well as a reduction in cardiovascular risk factors. The mechanisms seem to extend beyond the magnitude of weight loss alone and include improvements in incretin profiles, insulin secretion, and insulin sensitivity...
February 13, 2018: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/29420665/electroretinographic-evidence-suggesting-that-the-type-2-diabetic-retinopathy-of-the-sand-rat-psammomys-obesus-is-comparable-to-that-of-humans
#17
Ahmed Dellaa, Maha Benlarbi, Imane Hammoum, Nouha Gammoudi, Mohamed Dogui, Riadh Messaoud, Rached Azaiz, Ridha Charfeddine, Moncef Khairallah, Pierre Lachapelle, Rafika Ben Chaouacha-Chekir
PURPOSE: Type 2 diabetic retinopathy is the main cause of acquired blindness in adults. The aim of this work was to examine the retinal function of the sand rat Psammomys obesus as an animal model of diet-induced type 2 diabetes when subjected to a hypercaloric regimen. MATERIALS AND METHODS: Hyperglycemia was induced in Psammomys obesus by high caloric diet (4 kcal/g). The visual function of control (n = 7) and diabetic (n = 7) adult rodents were followed up during 28 consecutive weeks with full-field electroretinogram(ERG) recordings evoked to flashes of white light according to the standard protocol of the International Society for Clinical Electrophysiology of Vision protocol (ISCEV)...
2018: PloS One
https://www.readbyqxmd.com/read/29419487/genetically-engineered-pigs-as-models-for-human-disease
#18
REVIEW
Carolin Perleberg, Alexander Kind, Angelika Schnieke
Genetically modified animals are vital for gaining a proper understanding of disease mechanisms. Mice have long been the mainstay of basic research into a wide variety of diseases but are not always the most suitable means of translating basic knowledge into clinical application. The shortcomings of rodent preclinical studies are widely recognised, and regulatory agencies around the world now require preclinical trial data from nonrodent species. Pigs are well suited to biomedical research, sharing many similarities with humans, including body size, anatomical features, physiology and pathophysiology, and they already play an important role in translational studies...
January 22, 2018: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/29415997/downregulation-of-%C3%AE-1-4-galactosyltransferase-5-improves-insulin-resistance-by-promoting-adipocyte-commitment-and-reducing-inflammation
#19
Shu-Fen Li, Cui-Song Zhu, Yu-Meng Wang, Xin-Xin Xie, Liu-Ling Xiao, Zhi-Chun Zhang, Qi-Qun Tang, Xi Li
Protein glycosylation is an important post-translational modification. Aberrant glycosylation has been implicated in many diseases because of associated changes in protein distribution and biological function. We showed that the expression of β1, 4-galactosyltransferase 5 (B4GalT5) was positively correlated with diabetes and obesity. In vivo, B4GalT5 knockdown in subcutaneous adipose tissue alleviated insulin resistance and adipose tissue inflammation, and increased adipogenesis in high-fat diet (HFD)-fed mice and ob/ob mice...
February 7, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29413441/feasibility-evaluation-of-myocardial-cannabinoid-type-1-receptor-imaging%C3%A2-in%C3%A2-obesity-a-translational-approach
#20
Ines Valenta, Zoltan V Varga, Heather Valentine, Resat Cinar, Andrew Horti, William B Mathews, Robert F Dannals, Kimberley Steele, George Kunos, Richard L Wahl, Martin G Pomper, Dean F Wong, Pal Pacher, Thomas H Schindler
OBJECTIVES: The aim of this study was to evaluate the feasibility of targeted imaging of myocardial cannabinoid type 1 receptor (CB1-R) and its potential up-regulation in obese mice with translation to humans using [11C]-OMAR and positron emission tomography (PET)/computed tomography (CT). BACKGROUND: Activation of myocardial CB1-R by endocannabinoids has been implicated in cardiac dysfunction in diabetic mice. Obesity may lead to an up-regulation of myocardial CB1-R, potentially providing a mechanistic link between obesity and the initiation and/or progression of cardiomyopathy...
February 2018: JACC. Cardiovascular Imaging
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