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https://www.readbyqxmd.com/read/29778537/a-new-indanedione-derivative-alleviates-symptoms-of-diabetes-by-modulating-rage-nf-kappab-pathway-in-db-db-mice
#1
Gulnaz Khan, Meha Fatima Aftab, Bilquees Bano, Khalid Mohammed Khan, Munazza Murtaza, Sonia Siddiqui, M Hafizur Rehman, Rizwana Sanaullah Waraich
Accumulating evidence indicates that a number of tissues are damaged due to build-up of abnormal amount of Advanced Glycation End products (AGEs) in several diseases including diabetes. Currently AGE inhibitors are scarce in clinical use indicating a need for development of new anti-AGE agents. The aim of the current study is to identify the new AGE inhibitors and to decipher their mechanism of action for alleviating symptoms of diabetes in mice. Among several derivatives, one of the derivatives of indanedione, IDD-24 demonstrated highest inhibition of AGE formation and AGE mediated reactive oxygen species production in HepG-2 and mature 3T3-L1 adipocytes...
May 17, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29777831/microcystis-bloom-containing-microcystin-lr-induces-type-2-diabetes-mellitus
#2
Qiong Zhang, Wendi Qin, Liuyan Yang, Jing An, Xuxiang Zhang, Hao Hong, Lizhi Xu, Yaping Wang
Epidemiological data from Lake Taihu showed significantly higher incidences of type 2 diabetes mellitus (T2DM) than in other areas of China. This may be related to the occurrence of a Microcystis bloom in Lake Taihu in the summer and autumn every year. The objective of this study is to investigate whether the contaminated water from the Microcystis bloom and the derivative pollutant microcystin-LR (MC-LR) can explain the higher incidences of T2DM. Healthy male mice were fed with water from different regions of Lake Taihu, and were either acutely or chronically exposed to MC-LR through oral administration or intraperitoneal injection...
May 16, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29777745/serum-adiponectin-ferritin-ratio-in-relation-to-the-risk-of-type-2-diabetes-and-insulin-sensitivity
#3
Alex Aregbesola, Vanessa D F de Mello, Jaana Lindström, Sari Voutilainen, Jyrki K Virtanen, Sirkka Keinänen-Kiukaanniemi, Tomi-Pekka Tuomainen, Jaakko Tuomilehto, Uusitupa Matti
AIMS: Body iron inhibits the metabolism of adiponectin, an insulin sensitizing adipokine. We investigated the relationships of baseline and average of 4-year change in values of serum adiponectin (sA), serum ferritin (sF) and sA/sF ratio on type 2 diabetes (T2D) risk and insulin sensitivity (Matsuda ISI) and secretion (disposition index; DI30 ). METHODS: Prospective analyses were conducted in participants with impaired glucose tolerance of the Finnish Diabetes Prevention Study (n=516) recruited in 1993-1998...
May 16, 2018: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/29777696/sterilized-bifidobacteria-suppressed-fat-accumulation-and-blood-glucose-level
#4
Keita Kikuchi, Mahmoud Ben Othman, Kazuichi Sakamoto
Probiotics such as Lactobacillus and Bifidobacterium improve the balance of intestinal microflora and have various physiological functions beneficial to human health. It is not always known whether the ingested microbial cells are viable- or killed. However, even sterilized bacterial cells are functional. Bacterial cell functions are strain-specific and their modes of action are still poorly understood. The aim of this study was to elucidate the roles of sterilized bifidobacteria in obesity and lipid metabolism...
May 16, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29777582/comparative-study-of-liraglutide-and-insulin-glargine-on-glycemic-control-and-pancreatic-%C3%AE-cell-function-in-db-db-mice
#5
Yanli Li, Jia Zheng, Yunfeng Shen, Wangen Li, Meimei Liu, Jun Wang, Surong Zhu, Meihua Wu
BACKGROUND The aim of this study was to compare the effects of liraglutide, a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist, and insulin glargine, a long-acting insulin analog, on glycemic control and pancreatic β-cell function in db/db mice. MATERIAL AND METHODS Eight-week-old male db/db mice (n=40) were divided into five groups: the vehicle-treated group (VG) (n=8); the insulin glargine-treated group (GG) (dose, 450 mg/kg) (n=8), the low-dose liraglutide-treated group (LLG) (dose, 75 μg/kg) (n=8), the mid-dose liraglutide-treated group (MLG) (150 μg/kg) (n=8), and the high-dose liraglutide-treated group (HLG) (300 μg/kg) (n=8), treated with subcutaneous injection once daily, from 8-14 weeks-of-age...
May 19, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29777519/combination-glucose-lowering-therapy-plans-in-t2dm-case-based-considerations
#6
REVIEW
Lawrence Blonde, Susana Dipp, Daniel Cadena
Type 2 diabetes mellitus (T2DM) is a complex disease, and while lifestyle interventions remain the cornerstone of therapy, most patients will also require pharmacotherapy. Current diabetes treatment guidelines and algorithms recommend an individualized approach to setting glycemic goals and selecting treatment. Although a single antihyperglycemic agent may be appropriate as the initial T2DM pharmacotherapy, the progressive nature of the disease due to declining pancreatic β-cell function will result in the vast majority of T2DM patients eventually requiring two or more antihyperglycemic agents...
May 18, 2018: Advances in Therapy
https://www.readbyqxmd.com/read/29776493/mechanisms-in-bariatric-surgery-gut-hormones-diabetes-resolution-and-weight-loss
#7
Jens Juul Holst, Sten Madsbad, Kirstine N Bojsen-Møller, Maria Saur Svane, Nils Bruun Jørgensen, Carsten Dirksen, Christoffer Martinussen
Gastric bypass surgery leads to profound changes in the secretion of gut hormones with effects on metabolism, appetite, and food intake. Here, we discuss their contributions to the improvement in glucose tolerance and the weight loss that results from the operations. We find that the improved glucose tolerance is due the following events: a negative energy balance and resulting weight loss, which improve first hepatic and later peripheral insulin sensitivity, in combination with increased postprandial insulin secretion elicited particularly by exaggerated glucagon-like peptide-1 responses...
May 2018: Surgery for Obesity and related Diseases: Official Journal of the American Society for Bariatric Surgery
https://www.readbyqxmd.com/read/29774466/rs2227982-and-rs2227981-in-pdcd1-gene-are-functional-snps-associated-with-t1d-risk-in-east-asian
#8
Yong Gu, Lei Xiao, Wei Gu, Shu Chen, Yingjie Feng, Jian Wang, Zhixiao Wang, Yun Cai, Heng Chen, Xinyu Xu, Yun Shi, Mei Zhang, Kuanfeng Xu, Tao Yang
AIMS: To investigate whether PDCD1 gene polymorphisms are functional, and their associations with T1D risk and related clinical characteristics. METHODS: A total of 3060 Chinese Han individuals (1019 T1D patients and 2041 healthy controls) were genotyped for 4 tag single nucleotide polymorphisms (SNPs) within the PDCD1 region (rs2227982, rs7421861, rs10204525, and rs6710479) and another most studied synonymous SNP, rs2227981. In addition, 251 healthy individuals underwent an oral glucose tolerance test (OGTT); measures of insulin release and sensitivity were estimated from insulinogenic, BIGTT, Matsuda...
May 17, 2018: Acta Diabetologica
https://www.readbyqxmd.com/read/29773934/iglarlixi-a-new-once-daily-fixed-ratio-combination-of-basal-insulin-glargine-and-lixisenatide-for-the-management-of-type-2-diabetes
#9
Debbie Hinnen, Jodi Strong
Background: Patients with type 2 diabetes require treatment intensification to maintain glycemic control. Clinician reluctance, patient injection fears, hypoglycemia, weight gain, or other objections may lead to clinical inertia, whereby therapy is not intensified and patients live with uncontrolled hyperglycemia and increased risk for complications. Initiation of injectable therapy with a glucagon-like peptide (GLP)-1 receptor agonist and/or basal insulin is a recommended option for patients with type 2 diabetes inadequately controlled on one or more oral agents...
May 2018: Diabetes Spectrum: a Publication of the American Diabetes Association
https://www.readbyqxmd.com/read/29773932/effectiveness-and-tolerability-of-therapy-with-once-weekly-exenatide-versus-basal-insulin-among-injectable-naive-patients-with-type-2-diabetes-in-a-real-world-setting-in-the-united-states
#10
Anita M Loughlin, Qing Qiao, Anthony P Nunes, Stephen M Ezzy, Laura Yochum, C Robin Clifford, Robert V Gately, David D Dore, John D Seeger
A propensity-matched cohort study compared injectable-naive patients with type 2 diabetes initiating exenatide once weekly (EQW) or basal insulin (BI), from 2012 through 2015, within a U.S. electronic health record database. A1C and weight were obtained as observed or multiply imputed values at baseline and quarterly for 1 year (Q1-Q4). Hypoglycemia and gastrointestinal symptoms were identified using diagnostic codes and clinical notes. EQW ( n = 2,008) and BI ( n = 4,016) cohorts were comparable at baseline (mean A1C and weight: EQW, 8...
May 2018: Diabetes Spectrum: a Publication of the American Diabetes Association
https://www.readbyqxmd.com/read/29773801/lrrc8-vrac-anion-channels-enhance-%C3%AE-cell-glucose-sensing-and-insulin-secretion
#11
Till Stuhlmann, Rosa Planells-Cases, Thomas J Jentsch
Glucose homeostasis depends critically on insulin that is secreted by pancreatic β-cells. Serum glucose, which is directly sensed by β-cells, stimulates depolarization- and Ca2+ -dependent exocytosis of insulin granules. Here we show that pancreatic islets prominently express LRRC8A and LRRC8D, subunits of volume-regulated VRAC anion channels. Hypotonicity- or glucose-induced β-cell swelling elicits canonical LRRC8A-dependent VRAC currents that depolarize β-cells to an extent that causes electrical excitation...
May 17, 2018: Nature Communications
https://www.readbyqxmd.com/read/29773001/combined-administration-of-monosodium-glutamate-and-high-sucrose-diet-accelerates-the-induction-of-type-2-diabetes-vascular-dysfunction-and-memory-impairment-in-rats
#12
Kaja Saikrishna, Ringu Kumari, Kantamaneni Chaitanya, Subhankar Biswas, Pawan G Nayak, Jayesh Mudgal, Anoop Kishore, Krishnadas Nandakumar
In this study, we aimed to develop an experimental animal model for type 2 diabetes mellitus (T2DM) using a combination of monosodium glutamate (MSG) and high sucrose diet (HSD). Young male Wistar rats (20-30 g) were injected with MSG (2 or 4 mg/g, i.p. for 4 days). These rats were also fed an HSD, while the control group was fed a starch diet (SFD) for 150 days. Parameters assessed periodically were body weight, feed intake, blood glucose level, and oral glucose tolerance test (OGTT), lipid profile, liver and kidney function tests, skeletal muscle glucose uptake, cognitive function tests, and microvascular changes using isolated rat aorta...
2018: Journal of Environmental Pathology, Toxicology and Oncology
https://www.readbyqxmd.com/read/29771124/genistein-ameliorates-non-alcoholic-fatty-liver-disease-by-targeting-thromboxane-a2-pathway
#13
Wenzhe Wang, Junliang Chen, Jinyan Mao, Hongling Li, Mingfu Wang, Hao Zhang, Haitao Li, Wei Chen
Non-alcoholic fatty liver disease (NAFLD) is now a public health issue worldwide, but no drug has received approval yet. Genistein, an isoflavonoid derived from soybean, ameliorates high fat diet-induced NAFLD in mice, but the molecular underpinnings remain largely elusive. Arachidonic acid is a major ingredient of animal fats, and arachidonic acid cascade has been implicated in chronic inflammation. In this study, we investigated whether genistein against NAFLD by targeting arachidonic acid cascade. By using a mouse model, we showed that genistein supplementation improved high-fat diet induced NAFLD by normalizing hepatomegaly, liver steatosis, aminotransferase abnormalities and glucose tolerance...
May 17, 2018: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/29770924/roux-en-y-gastric-bypass-surgery-induced-weight-loss-and-metabolic-improvements-are-similar-in-tgr5-deficient-and-wildtype-mice
#14
Zheng Hao, R Leigh Townsend, Michael B Mumphrey, Thomas W Gettys, Sangho Yu, Heike Münzberg, Christopher D Morrison, Hans-Rudolf Berthoud
BACKGROUND AND PURPOSE: Roux-en-Y gastric bypass surgery (RYGB) remains one of the most effective treatments for obesity and type 2 diabetes. Despite this, the mechanisms through which it acts are still not well understood. Bile acid signaling through the transmembrane G-protein-coupled receptor TGR5 has been shown to have significant effects on metabolism and has recently been reported to be necessary for the full effects of vertical sleeve gastrectomy (VSG), a bariatric surgery with similar effects to RYGB...
May 16, 2018: Obesity Surgery
https://www.readbyqxmd.com/read/29770126/crosstalk-between-the-unfolded-protein-response-micrornas-and-insulin-signaling-pathways-in-search-of-biomarkers-for-the-diagnosis-and-treatment-of-type-2-diabetes
#15
REVIEW
Chinar Berry, Megha Lal, B K Binukumar
Type 2 diabetes mellitus (T2DM) is a metabolic disorder that is characterized by functional defects in glucose metabolism and insulin secretion. Its complex etiology and multifaceted nature have made it difficult to design effective therapies for early diagnosis and treatment. Several lines of evidence indicate that aberrant activation of the unfolded protein response (UPR) in response to endoplasmic reticulum (ER) stress impairs the β cell's ability to respond to glucose and promotes apoptosis. Elucidating the molecular mechanisms that govern β cell dysfunction and cell death can help investigators design therapies to halt or prevent the development of T2DM...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29769449/fatty-acid-receptor-modulator-pbi-4050-inhibits-kidney-fibrosis-and-improves-glycemic-control
#16
Yan Li, Sungjin Chung, Zhilian Li, Jessica M Overstreet, Lyne Gagnon, Brigitte Grouix, Martin Leduc, Pierre Laurin, Ming-Zhi Zhang, Raymond C Harris
Extensive kidney fibrosis occurs in several types of chronic kidney diseases. PBI-4050, a potentially novel first-in-class orally active low-molecular weight compound, has antifibrotic and antiinflammatory properties. We examined whether PBI-4050 affected the progression of diabetic nephropathy (DN) in a mouse model of accelerated type 2 diabetes and in a model of selective tubulointerstitial fibrosis. eNOS-/- db/db mice were treated with PBI-4050 from 8-20 weeks of age (early treatment) or from 16-24 weeks of age (late treatment)...
May 17, 2018: JCI Insight
https://www.readbyqxmd.com/read/29769329/isolation-of-state-dependent-monoclonal-antibodies-against-the-12-transmembrane-domain-glucose-transporter-4-using-virus-like-particles
#17
David F Tucker, Jonathan T Sullivan, Kimberly-Anne Mattia, Christine R Fisher, Trevor Barnes, Manu N Mabila, Rona Wilf, Chidananda Sulli, Meghan Pitts, Riley J Payne, Moniquetta Hall, Duncan Huston-Paterson, Xiaoxiang Deng, Edgar Davidson, Sharon H Willis, Benjamin J Doranz, Ross Chambers, Joseph B Rucker
The insulin-responsive 12-transmembrane transporter GLUT4 changes conformation between an inward-open state and an outward-open state to actively facilitate cellular glucose uptake. Because of the difficulties of generating conformational mAbs against complex and highly conserved membrane proteins, no reliable tools exist to measure GLUT4 at the cell surface, follow its trafficking, or detect the conformational state of the protein. Here we report the isolation and characterization of conformational mAbs that recognize the extracellular and intracellular domains of GLUT4, including mAbs that are specific for the inward-open and outward-open states of GLUT4...
May 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29768504/sarcopoterium-spinosum-extract-improved-insulin-sensitivity-in-mice-models-of-glucose-intolerance-and-diabetes
#18
Konstantin Rozenberg, Tovit Rosenzweig
BACKGROUND: The glucose lowering properties of Sarcopoterium spinosum, a traditional medicinal plant, were previously validated by us using KK-Ay mice as a genetic model for type 2 diabetes (T2D). OBJECTIVE: To clarify the effects of Sarcopoterium spinosum extract (SSE) on diet-induced glucose intolerance and to investigate SSE effects on carbohydrate and lipid metabolism in target tissues of both high-fat-diet (HFD)-fed and KK-Ay mice. RESULTS: Mice were given SSE (70 mg/day) for 6 weeks...
2018: PloS One
https://www.readbyqxmd.com/read/29768196/loss-of-abhd15-impairs-the-anti-lipolytic-action-of-insulin-by-altering-pde3b-stability-and-contributes-to-insulin-resistance
#19
Wenmin Xia, Ariane R Pessentheiner, Dina C Hofer, Melina Amor, Renate Schreiber, Gabriele Schoiswohl, Thomas O Eichmann, Evelyn Walenta, Bianca Itariu, Gerhard Prager, Hubert Hackl, Thomas Stulnig, Dagmar Kratky, Thomas Rülicke, Juliane G Bogner-Strauss
Elevated circulating fatty acids (FAs) contribute to obesity-associated metabolic complications, but the mechanisms by which insulin suppresses lipolysis are poorly understood. We show that α/β-hydrolase domain-containing 15 (ABHD15) is required for the anti-lipolytic action of insulin in white adipose tissue (WAT). Neither insulin nor glucose treatments can suppress FA mobilization in global and conditional Abhd15-knockout (KO) mice. Accordingly, insulin signaling is impaired in Abhd15-KO adipocytes, as indicated by reduced AKT phosphorylation, glucose uptake, and de novo lipogenesis...
May 15, 2018: Cell Reports
https://www.readbyqxmd.com/read/29766635/efficacy-and-safety-of-mk-1293-insulin-glargine-compared-with-originator-insulin-glargine-lantus-in-type-1-diabetes-a-randomized-open-label-clinical-trial
#20
Philip D Home, Raymond L H Lam, Wendy L Carofano, Gregory T Golm, Roy Eldor, Michael F Crutchlow, Michael C Marcos, Julio Rosenstock, Priscilla A Hollander, Baptist Gallwitz
AIMS: Comparison of the efficacy and safety of MK-1293 insulin glargine (Mk-Gla; 100 U/ml) with originator insulin glargine, Lantus (Sa-Gla) in people with type 1 diabetes mellitus (T1DM). MATERIALS AND METHODS: This phase 3, randomized, active-controlled, open-label, 52-week study enrolled 508 people with T1DM (HbA1c ≤ 11.0%; 97 mmol/mol) taking basal and prandial insulin. Participants were randomized 1:1 to once-daily Mk-Gla (n=245) or Sa-Gla (n=263). Dose titration of basal insulin was by a pre-breakfast plasma glucose dosing algorithm...
May 15, 2018: Diabetes, Obesity & Metabolism
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