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https://www.readbyqxmd.com/read/28925030/drug-repurposing-may-generate-novel-approaches-to-treating-depression
#1
REVIEW
Mohamed Elsaed Ebada
OBJECTIVES: The breakthrough advancements in scientific medical research have greatly improved our understanding of the pathogenesis of depression, encouraging drug discoverers to take a shorter path than ever through drug repurposing to generate new antidepressant medications. In addition to reduced noradrenergic and serotonergic neurotransmission in the brain, other coincidence features such as glutamate neurotoxicity, inflammation and/or cerebrovascular insufficiency are implicated in the pathogenesis of major depressive disorder and late-life depression...
September 18, 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/28921908/biphasic-insulin-aspart-30-reduces-glycemic-variability-to-a-greater-degree-than-insulin-detemir-a-randomized-controlled-trial-of-once-daily-insulin-regimens-using-continuous-glucose-monitoring
#2
Daisuke Tsujino, Rimei Nishimura, Yoshiko Onda, Chiaki Seo, Kiyotaka Ando, Kazunori Utsunomiya
INTRODUCTION: We compared the efficacy of insulin detemir and biphasic insulin aspart-30 given in the morning as an add-on to oral hypoglycemic agents (OHAs) in type 2 diabetic patients. MATERIALS AND METHODS: This study enrolled 30 patients with poorly controlled type 2 diabetes (8%≤HbA1c<11%) being treated with OHA mono- or combination therapy with biguanides, sulfonylureas, or thiazolidinediones. The patients were randomly assigned to insulin detemir (group D) or insulin aspart-30 (group A) given in the morning as add-on to OHAs...
September 16, 2017: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/28918342/the-potential-effect-of-ultra-long-insulin-degludec-on-glycemic-variability
#3
REVIEW
M Rodacki, R M Carvalho, L Zajdenverg
Despite the therapeutic advances in the treatment of diabetes, metabolic control instability due to glycemic variability (GV) is frequently observed in patients with diabetes on intensive insulin therapy and is associated with hyperglycemic peaks and hypoglycemic episodes. Hyperglycemia associated with GV has been implicated in the development of chronic complications due to its pro-oxidative consequences. On the other hand, hypoglycemia can be associated with increased cardiovascular risk secondarily to adrenergic activation...
June 30, 2017: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/28916541/a-proteomic-atlas-of-insulin-signalling-reveals-tissue-specific-mechanisms-of-longevity-assurance
#4
Luke S Tain, Robert Sehlke, Chirag Jain, Manopriya Chokkalingam, Nagarjuna Nagaraj, Paul Essers, Mark Rassner, Sebastian Grönke, Jenny Froelich, Christoph Dieterich, Matthias Mann, Nazif Alic, Andreas Beyer, Linda Partridge
Lowered activity of the insulin/IGF signalling (IIS) network can ameliorate the effects of ageing in laboratory animals and, possibly, humans. Although transcriptome remodelling in long-lived IIS mutants has been extensively documented, the causal mechanisms contributing to extended lifespan, particularly in specific tissues, remain unclear. We have characterized the proteomes of four key insulin-sensitive tissues in a long-lived Drosophila IIS mutant and control, and detected 44% of the predicted proteome (6,085 proteins)...
September 15, 2017: Molecular Systems Biology
https://www.readbyqxmd.com/read/28904276/a-case-of-acromegaly-in-which-a-pituitary-gland-tumor-was-reduced-significantly-by-administering-octreotide-long-acting-release-lar-and-could-be-removed-surgically
#5
Tadashi Arao, Yosuke Okada, Fumi Uemura, Shigeru Nishizawa, Yoshiya Tanaka
A 54-year-old woman was admitted to our hospital for detailed examination of acromegaly because she noticed bilateral hand and finger swelling at the age of 43 and plantar thickening, facial changes and unclear articulation at the age of 49. She had prominent brow ridges, mandibular protrusion, and enlargement of the hands, feet, nasal wings, lips and tongue. Her growth hormone (GH) level was 39.8 ng/ml, insulin-like growth factor-1 (IGF-1) level was 717 ng/ml, GH level was not suppressed (22.9 ng/ml) during a 75-g oral glucose tolerance test (OGTT)...
2017: Journal of UOEH
https://www.readbyqxmd.com/read/28890700/dietary-capsaicin-improves-glucose-homeostasis-and-alters-the-gut-microbiota-in-obese-diabetic-ob-ob-mice
#6
Jun-Xian Song, Hui Ren, Yuan-Feng Gao, Chong-You Lee, Su-Fang Li, Feng Zhang, Long Li, Hong Chen
Background: The effects of capsaicin on obesity and glucose homeostasis are still controversial and the mechanisms underlying these effects remain largely unknown. This study aimed to investigate the potential relationship between the regulation of obesity and glucose homeostasis by dietary capsaicin and the alterations of gut microbiota in obese diabetic ob/ob mice. Methods: The ob/ob mice were subjected to a normal, low-capsaicin (0.01%), or high-capsaicin (0.02%) diet for 6 weeks, respectively. Obesity phenotypes, glucose homeostasis, the gut microbiota structure and composition, short-chain fatty acids, gastrointestinal hormones, and pro-inflammatory cytokines were measured...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28887275/ffa4-gpr120-as-a-fatty-acid-sensor-involved-in-appetite-control-insulin-sensitivity-and-inflammation-regulation
#7
REVIEW
Dong-Soon Im
Unsaturated long-chain fatty acids have been suggested to be beneficial in the context of cardiovascular disorders based in epidemiologic studies conducted in Greenland and Mediterranean. DHA and EPA are omega-3 polyunsaturated fatty acids that are plentiful in fish oil, and oleic acid is an omega-9 monounsaturated fatty acid, rich in olive oil. Dietary intake of these unsaturated long-chain fatty acids have been associated with insulin sensitivity and weight loss, which contrasts with the impairment of insulin sensitivity and weight gain associated with high intakes of saturated long-chain fatty acids...
September 8, 2017: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/28870245/mice-overexpressing-growth-hormone-exhibit-increased-skeletal-muscle-myostatin-and-murf1-with-attenuation-of-muscle-mass
#8
Leslie A Consitt, Alicson Saneda, Gunjan Saxena, Edward O List, John J Kopchick
BACKGROUND: In contrast to the acute effects of growth hormone (GH) on skeletal muscle protein synthesis, long-term GH treatment appears to have negligible effects on muscle mass. Despite this knowledge, little is known regarding the chronic effects of GH on skeletal muscle protein synthesis and atrophy signaling pathways. The purpose of this study was to determine if protein synthesis pathways are attenuated and/or muscle atrophy intracellular signaling pathways are altered in the skeletal muscle of transgenic bovine GH (bGH) mice...
September 4, 2017: Skeletal Muscle
https://www.readbyqxmd.com/read/28864965/pharmacological-management-of-gestational-diabetes-mellitus
#9
Geetha Mukerji, Denice S Feig
Gestational diabetes mellitus (GDM) is associated with an increased risk of adverse pregnancy outcomes in the setting of poor glycemic control. The initial management for GDM includes intensive lifestyle modification, which often requires behavioral and nutritional changes to optimize glycemic control. Pharmacotherapy for GDM is initiated when glycemic targets are not met. The rapid-acting bolus analogues aspart and lispro achieve postprandial targets with less hypoglycemia compared to regular insulin, with similar fetal outcomes...
September 2, 2017: Drugs
https://www.readbyqxmd.com/read/28864157/basal-insulin-for-the-management-of-diabetic-ketoacidosis
#10
REVIEW
Leonid Barski, Evgenia Brandstaetter, Iftach Sagy, Alan Jotkowitz
Due to its pharmacokinetic properties, it has been suggested that long-acting insulin analogues may have a role in facilitating the transition from continuous intravenous insulin infusion to subcutaneous maintenance therapy in patients with DKA for prevention of rebound hyperglycemia, particularly if there are high insulin requirements. Concomitant administration of basal insulin analogues with regular insulin infusion accelerates ketoacidosis resolution and prevents rebound hyperglycemia. Several studies have investigated the use of basal insulin in the management of DKA...
August 30, 2017: European Journal of Internal Medicine
https://www.readbyqxmd.com/read/28859418/merging-the-morphology-performance-fitness-paradigm-and-life-history-theory-in-the-eagle-lake-garter-snake-research-project
#11
Elizabeth A Addis, Eric J Gangloff, Maria G Palacios, Katherine E Carr, Anne M Bronikowski
The morphology-performance-fitness paradigm for testing selection on morphological traits has seen decades of successful application. At the same time, life-history approaches using matrix methods and perturbation studies have also allowed the direct estimate of selection acting on vital rates and the traits that comprise them. Both methodologies have been successfully applied to the garter snakes of the long-term Eagle Lake research project to reveal selection on morphology, such as color pattern, number of vertebrae, and gape size; and life-history traits such as birth size, growth rates, and juvenile survival...
August 1, 2017: Integrative and Comparative Biology
https://www.readbyqxmd.com/read/28831150/glp-1-exendin-4-induces-%C3%AE-cell-proliferation-via-the-epidermal-growth-factor-receptor
#12
Joseph Fusco, Xiangwei Xiao, Krishna Prasadan, Qingfeng Sheng, Congde Chen, Yung-Ching Ming, George Gittes
Exendin-4 is a long acting glucagon-like peptide 1 (GLP-1) analogue that is an agonist for the GLP-1 receptor, a G-protein coupled receptor (GPCR). Exendin-4 is used to clinically improve glucose tolerance in diabetic patients due to its ability to enhance insulin secretion. In rodents, and possibly in humans, exendin-4 can stimulate β-cell proliferation. The exact mechanism of action to induce β-cell proliferation is not well understood. Here, using a β-cell specific epidermal growth factor receptor (EGFR) null mouse, we show that exendin-4 induced an increase in proliferation and β-cell mass through EGFR...
August 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28827839/lean-diabetes-in-middle-aged-adults-a-joint-analysis-of-the-german-dive-and-dpv-registries
#13
Bettina Hartmann, Stefanie Lanzinger, Peter Bramlage, Felix Groß, Thomas Danne, Siegfried Wagner, Dietmar Krakow, Artur Zimmermann, Christian Malcharzik, Reinhard W Holl
AIMS: To assess differences in demographics, treatment and outcome of lean (LD) compared to overweight and obese people with diabetes clinically classified as type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: We combined data from the German DIVE (Diabetes Versorgungs-Evaluation) and DPV (Diabetes-Patienten-Verlaufsdokumentation) databases to produce a large cohort of people with T2DM. The characteristics of people with Body Mass Index (BMI) <25 kg/m2, ≥25-30 kg/m2 and ≥30 kg/m2 aged 30 to 50 years were compared, including demographics, cardiovascular (CV) risk factors, comorbidities and outcomes...
2017: PloS One
https://www.readbyqxmd.com/read/28816532/comparing-clinical-outcomes-and-costs-for-different-treatment-intensification-approaches-in-patients-with-type-2-diabetes-uncontrolled-on-basal-insulin-adding-glucagon-like-peptide-1-receptor-agonists-vs-adding-rapid-acting-insulin-or-increasing-basal-insulin
#14
Philip Levin, Tao Fan, Xue Song, Damion Nero, Brian Davis, Bong-Chul Chu
Objective-Not all patients with type 2 diabetes achieve the recommended glycated hemoglobin A1c (A1C) levels after adequate titration of basal insulin (BI). Current intensification approaches include addition of rapid-acting insulin (RAI) or a glucagon-like peptide-1 receptor agonist (GLP-1 RA), but it is not clear which strategy results in better long-term outcomes. Methods-This retrospective analysis of health insurance claims data in the US MarketScan database compared glycemic control and healthcare resource utilization and costs 12 months after adding GLP-1 RA to BI vs adding RAI or increasing BI doses...
August 17, 2017: Endocrine Practice
https://www.readbyqxmd.com/read/28794173/glucose-potentiates-%C3%AE-cell-function-by-inducing-tph1-expression-in-rat-islets
#15
Yuqing Zhang, Ruyuan Deng, Xue Yang, Wan Xu, Yun Liu, Fengying Li, Juan Zhang, Hongju Tang, Xueying Ji, Yufang Bi, Xiao Wang, Libin Zhou, Guang Ning
Impaired pancreatic β-cell function is the primary defect in type 2 diabetes. Glucose is an important regulator of β-cell growth and function; however, the mechanisms that are involved in the chronic adaptation of β-cells to hyperglycemia remain largely unknown. In the present study, global gene expression patterns revealed that tryptophan hydroxylase 1 (Tph1) was the most profound of genes that are up-regulated in rat islets exposed to high glucose. Calcium and cAMP signals synergistically mediated glucose-stimulated Tph1 transcription in β-cells by activating cAMP-responsive element-binding protein and promoting its binding with a Tph1 promoter...
August 9, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28792863/addition-of-insulin-to-parenteral-nutrition-for-control-of-hyperglycemia
#16
Adam McCulloch, Vishakha Bansiya, Jeremy M Woodward
Administration of parenteral nutrition (PN) may result in hyperglycemia in patients with preexisting diabetes or disease-related insulin resistance, and it can be associated with increased rates of complications. Treatment requires insulin therapy. Insulin can be administered subcutaneously, intravenously via a variable rate sliding scale, or by adding it directly to the PN. The last method is a potentially attractive technique for a number of reasons-it could deliver the insulin intravenously at a steady rate alongside carbohydrates, and in malnourished patients with little subcutaneous tissue, it may prevent the need for frequent insulin injections...
August 1, 2017: JPEN. Journal of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/28780057/top-down-mass-spectrometric-immunoassay-for-human-insulin-and-its-therapeutic-analogs
#17
Dobrin Nedelkov, Eric E Niederkofler, Paul E Oran, Scott Peterman, Randall W Nelson
Measurement of insulin and its therapeutic analogs is important in diabetes, hypoglycemia, sports anti-doping and toxicology. Commercial insulin immunoassays fail to detect commonly prescribed insulin analogs. Because of their unique sequences and masses, these analogs are readily measured and distinguished with mass spectrometric (MS) assays. Reviewed here is an insulin mass spectrometric immunoassay (MSIA) that combines micro-scale immunoaffinity capture with sensitive MS detection of insulin and its therapeutic analogs...
August 3, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28774890/mir-338-controls-bpa-triggered-pancreatic-islets-insulin-secretory-dysfunction-from-compensation-to-decompensation-by-targeting-pdx-1
#18
Jie Wei, Dongxiao Ding, Tao Wang, Qiong Liu, Yi Lin
Bisphenol A (BPA) can disrupt glucose homeostasis and impair pancreatic islet function; however, the mechanisms behind these effects are poorly understood. Male mice (4 wk old) were treated with BPA (50 or 500 μg/kg/day) for 8 wk. Whole-body glucose homeostasis, pancreatic islet morphology and function, and miR-338-mediated molecular signal transduction analyses were examined. We showed that BPA treatment led to a disruption of glucose tolerance and a compensatory increase of pancreatic islets insulin secretion and pancreatic and duodenal homeobox 1 (Pdx1) expression in mice...
August 3, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28767190/insulin-degludec-in-the-first-trimester-of-pregnancy-report-of-two-cases
#19
Agostino Milluzzo, Andrea Tumminia, Nunzio M Scalisi, Lucia Frittitta, Riccardo Vigneri, Laura Sciacca
Insulin degludec is an extra-long-acting insulin analog that allows for enhanced efficacy and flexibility in the injection time. However, it is not approved for use during pregnancy. We report the pregnancy outcome and newborn conditions in two type 1 diabetic women who continued pre-conception degludec treatment during embryogenesis. No pregnancy complication or congenital neonatal malformation was observed. Both babies presented with hypoglycemia and required neonatal intensive care unit admission. Degludec treatment did not cause adverse effects in the mothers or malformations in the newborns...
August 2, 2017: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/28762200/rapid-acting-and-human-insulins-hexamer-dissociation-kinetics-upon-dilution-of-the-pharmaceutical-formulation
#20
Klaus Gast, Anja Schüler, Martin Wolff, Anja Thalhammer, Harald Berchtold, Norbert Nagel, Gudrun Lenherr, Gerrit Hauck, Robert Seckler
PURPOSE: Comparison of the dissociation kinetics of rapid-acting insulins lispro, aspart, glulisine and human insulin under physiologically relevant conditions. METHODS: Dissociation kinetics after dilution were monitored directly in terms of the average molecular mass using combined static and dynamic light scattering. Changes in tertiary structure were detected by near-UV circular dichroism. RESULTS: Glulisine forms compact hexamers in formulation even in the absence of Zn(2+)...
July 31, 2017: Pharmaceutical Research
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