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https://www.readbyqxmd.com/read/28551803/insulin-resistance-and-mitochondrial-dysfunction
#1
Alba Gonzalez-Franquesa, Mary-Elizabeth Patti
Insulin resistance precedes and predicts the onset of type 2 diabetes (T2D) in susceptible humans, underscoring its important role in the complex pathogenesis of this disease. Insulin resistance contributes to multiple tissue defects characteristic of T2D, including reduced insulin-stimulated glucose uptake in insulin-sensitive tissues, increased hepatic glucose production, increased lipolysis in adipose tissue, and altered insulin secretion. Studies of individuals with insulin resistance, both with established T2D and high-risk individuals, have consistently demonstrated a diverse array of defects in mitochondrial function (i...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28551774/continuous-glucose-monitoring-for-patients-with-type-1-diabetes-on-multiple-daily-injections-of-insulin-pros-and-cons
#2
Maria Ida Maiorino, Michela Petrizzo, Giuseppe Bellastella, Katherine Esposito
Continuous glucose monitoring associated with intensive insulin regimens represents a useful tool to lower HbA1c in selected adults with type 1 diabetes. Recent randomized controlled trials demonstrated greater glycemic benefits in type 1 diabetic patients treated with multiple daily injections of insulin and continuous glucose monitoring over usual care. These positive outcomes, however, are counter-balanced by several limitations that restrict the use of continuous glucose monitoring in the real life, including the apparent lack of benefits in children and pregnant diabetic women, the high cost, the stringent patients' selection, and the presence of a multi-disciplinary team with specific expertise...
May 27, 2017: Endocrine
https://www.readbyqxmd.com/read/28551720/effect-of-paricalcitol-on-pancreatic-oxidative-stress-inflammatory-markers-and-glycemic-status-in-diabetic-rats
#3
T M Ali, B El Esawy, A Elaskary
OBJECTIVES: This study is designed to explore the effect of paricalcitol (vitamin D receptor agonist) on pancreatic oxidative stress, inflammatory markers, and adiponectin and glycemic status in diabetic rats. MATERIALS AND METHODS: Forty Sprague-Dawley male rats aged 10-12 weeks (150-250 g) were used in this study. Type 2 diabetes was developed by providing 4 weeks of high-fat-diet feeding before one shot of streptozotocin injection (40 mg/kg i.p.). Four study groups were designed as normal control rats, diabetic control vehicle-treated, diabetic paricalcitol-treated (0...
May 27, 2017: Irish Journal of Medical Science
https://www.readbyqxmd.com/read/28551699/the-role-of-somatostatin-in-glp-1-induced-inhibition-of-glucagon-secretion-in-mice
#4
Anne Ørgaard, Jens J Holst
AIMS/HYPOTHESIS: Glucagon-like peptide-1 (GLP-1) receptor agonists are currently used for the treatment of type 2 diabetes. Their main mechanism of action is enhancement of glucose-induced insulin secretion (from increased beta cell glucose sensitivity) and inhibition of glucagon secretion. The latter has been demonstrated to account for about half of their blood glucose-lowering activity. Whereas the effect of GLP-1 on insulin secretion is clearly dependent on ambient glucose concentrations and has been described in detail, the mechanism responsible for the inhibitory effect of GLP-1 on glucagon secretion is heavily debated...
May 27, 2017: Diabetologia
https://www.readbyqxmd.com/read/28551698/glucose-metabolism-during-rotational-shift-work-in-healthcare-workers
#5
Anu Sharma, Marcello C Laurenti, Chiara Dalla Man, Ron T Varghese, Claudio Cobelli, Robert A Rizza, Aleksey Matveyenko, Adrian Vella
AIMS/HYPOTHESIS: Shift-work is associated with circadian rhythm disruption and an increased risk of obesity and type 2 diabetes. We sought to determine the effect of rotational shift-work on glucose metabolism in humans. METHODS: We studied 12 otherwise healthy nurses performing rotational shift-work using a randomised crossover study design. On each occasion, participants underwent an isotope-labelled mixed meal test during a simulated day shift and a simulated night shift, enabling simultaneous measurement of glucose flux and beta cell function using the oral minimal model...
May 27, 2017: Diabetologia
https://www.readbyqxmd.com/read/28551627/the-cooh-terminus-of-the-igf-1ec-isoform-enhances-the-proliferation-and-migration-of-human-mcf-7-breast-cancer-cells
#6
Panagiotis F Christopoulos, Efstathia Papageorgiou, Constantina Petraki, Michael Koutsilieris
BACKGROUND/AIM: The insulin-like growth factor-1 (IGF-1) signaling is well implicated in cancer biology, however the potential roles of the distinct IGF-1 isoforms in human malignancies are largely unknown. Recently, the carboxyl-terminal of the IGF-1Ec variant (hEc; 24aa) has been associated with osteosarcoma and prostate cancer. Herein, we investigated the potential role of hEc in breast cancer. MATERIALS AND METHODS: Synthetic hEc peptide was administrated to MCF-7 and MDA-MB-231 breast cancer cells...
June 2017: Anticancer Research
https://www.readbyqxmd.com/read/28551552/standardized-mori-ramulus-extract-improves-insulin-secretion-and-insulin-sensitivity-in-c57blks-j-db-db-mice-and-ins-1-cells
#7
Soo-Yeon Park, Bora Jin, Jae-Ho Shin, Sirichai Adisakwattana, Oran Kwon
Abnormalities in the hyperbolic relationship between insulin sensitivity and insulin secretion may cause oxidative stress and non-enzymatic glycation, resulting in an increased risk of type 2 diabetes. Here, we performed a 14-week study to investigate the effects of ethanolic extract of Mori ramulus (MRE; 0, 800, and 1600mg/kg body weight) and its signature component oxyresveratrol (OXY; 800mg/kg body weight) on β-cell dysfunction and insulin resistance in C57BLKS/J db/db mice fed with a high-fat diet. Compared with the diabetic control group, the high-dose MRE group showed a significant decrease in fasting blood glucose (p=0...
May 25, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28551162/association-of-sympathovagal-imbalance-with-cognitive-impairment-in-type-2-diabetes
#8
Pal Auroprajna, Basanta Manjari Naik, Jaya Prakash Sahoo, Gorantla Shravya Keerthi, Manohar Pavanya, Gopal Krushna Pal
OBJECTIVE: Sympathovagal imbalance (SVI) has been reported to be associated with metabolic derangements in type 2 diabetes. We investigated the association of SVI with cognitive impairment in patients with type 2 diabetes. METHODS: Patients with a new diagnosis of type 2 diabetes (n=43) and age-matched healthy control subjects (n=43) were recruited for the study. Body mass index and blood pressure measurements were recorded. SVI was assessed by spectral analysis of heart rate variability (HRV), and cognitive function was assessed by recording the positive wave that appears in 300 milliseconds from application of stimulus in event-related potential tracing (P300)...
May 24, 2017: Canadian Journal of Diabetes
https://www.readbyqxmd.com/read/28550730/transplantation-of-aire-overexpressing-bone-marrow-derived-dendritic-cells-delays-the-onset-of-type-1-diabetes
#9
Dongbei Li, Bo Zhao, Yadong Luo, Steven Limbara, Bingjie Zhao, Xueyang Zou, Wei Yang, Yi Li
Autoimmune regulator (Aire) plays an indispensable role in maintaining central immune tolerance by promoting the ectopic expression of tissue-restricted antigens (TRAs) in medullary thymic epithelial cells (mTECs) and dendritic cells (DCs), which lead to the deletion of autoreactive T cells or the induction of Tregs and consequently prevent autoimmune disease development. Curing autoimmune diseases has always been a challenge. DC-based immunotherapy represents a new and effective method to establish tolerance...
May 24, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28550517/early-prediction-of-autoimmune-type-1-diabetes
#10
REVIEW
Simon E Regnell, Åke Lernmark
Underlying type 1 diabetes is a genetic aetiology dominated by the influence of specific HLA haplotypes involving primarily the class II DR-DQ region. In genetically predisposed children with the DR4-DQ8 haplotype, exogenous factors, yet to be identified, are thought to trigger an autoimmune reaction against insulin, signalled by insulin autoantibodies as the first autoantibody to appear. In children with the DR3-DQ2 haplotype, the triggering reaction is primarily against GAD signalled by GAD autoantibodies (GADA) as the first-appearing autoantibody...
May 26, 2017: Diabetologia
https://www.readbyqxmd.com/read/28550295/effects-of-protein-corona-on-iapp-amyloid-aggregation-fibril-remodelling-and-cytotoxicity
#11
Emily H Pilkington, Yanting Xing, Bo Wang, Aleksandr Kakinen, Miaoyi Wang, Thomas P Davis, Feng Ding, Pu Chun Ke
Aggregation of islet amyloid polypeptide (IAPP), a peptide hormone co-synthesized and co-stored with insulin in pancreatic cells and also co-secreted to the circulation, is associated with beta-cell death in type-2 diabetes (T2D). In T2D patients IAPP is found aggregating in the extracellular space of the islets of Langerhans. Although the physiological environments of these intra- and extra-cellular compartments and vascular systems significantly differ, the presence of proteins is ubiquitous but the effects of protein binding on IAPP aggregation are largely unknown...
May 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28550272/non-alcoholic-fatty-liver-disease-a-chronic-disease-of-the-21-st-century
#12
Metrakos Peter, Nilsson Tommy
Non-alcoholic fatty liver disease (NAFLD) comprises a spectrum of metabolic states ranging from simple steatosis to inflammation with associated fibrosis to cirrhosis. Though accumulation of hepatic fat is not associated with a significant increase in mortality rates, hepatic inflammation is, as this augments the risk of terminal liver disease, i.e., cirrhosis, hepatic decompensation (liver failure) and/or hepatocellular carcinoma. Disease progression is usually slow, over a decade or more and, for the most part, remains asymptomatic...
May 26, 2017: Journal of Biomedical Research
https://www.readbyqxmd.com/read/28550243/apomorphine-therapy-for-neuronal-insulin-resistance-in-a-mouse-model-of-alzheimer-s-disease
#13
Norimichi Nakamura, Yasumasa Ohyagi, Tomohiro Imamura, Yuki T Yanagihara, Kyoko M Iinuma, Naoko Soejima, Hiroyuki Murai, Ryo Yamasaki, Jun-Ichi Kira
Apomorphine (APO) promotes intraneuronal amyloid-β (Aβ) degradation and improves memory function in an Alzheimer's disease (AD) model, 3xTg-AD mice. Since insulin resistance is increased in AD neurons, we investigated the effects of APO on brain insulin resistance in 3xTg-AD mice at early and late stages. After 1-month subcutaneous injection of Apokyn® to 3xTg-AD mice at 6 or 12 months of age, memory function was significantly improved in both age groups. Protein levels of insulin-degrading enzyme (IDE), which is linked to insulin signaling and degrades Aβ, significantly increased in the 3xTg-AD mice brain compared with non-transgenic mice, and were further increased by APO...
May 25, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28550194/the-risk-of-severe-hypoglycemia-in-type-1-diabetes-over-30-years-of-follow-up-in-the-dcct-edic-study
#14
Rose A Gubitosi-Klug, Barbara H Braffett, Neil H White, Robert S Sherwin, F John Service, John M Lachin, William V Tamborlane
OBJECTIVE: During the DCCT, intensive diabetes therapy achieving a mean HbA1c of ∼7% was associated with a threefold increase in the rate of severe hypoglycemia (defined as requiring assistance) compared with conventional diabetes therapy with a mean HbA1c of 9% (61.2 vs. 18.7 per 100 patient-years). After ∼30 years of follow-up, we investigated the rates of severe hypoglycemia in the DCCT/EDIC cohort. RESEARCH DESIGN AND METHODS: Rates of severe hypoglycemia were reported quarterly during DCCT and annually during EDIC (i...
May 26, 2017: Diabetes Care
https://www.readbyqxmd.com/read/28549828/deficiency-of-long-isoforms-of-nfe2l1-sensitizes-min6-pancreatic-%C3%AE-cells-to-arsenite-induced-cytotoxicity
#15
Qi Cui, Jingqi Fu, Yuxin Hu, Yongfang Li, Bei Yang, Lu Li, Jing Sun, Chengjie Chen, Guifan Sun, Yuanyuan Xu, Qiang Zhang, Jingbo Pi
Increasing evidence indicates that chronic inorganic arsenic exposure is associated with type 2 diabetes (T2D), a disease of growing prevalence. Pancreatic β-cells were targeted and damaged by oxidative stress induced by arsenite. We previously showed that nuclear factor erythroid 2 like 2 (Nfe2l2)-deficient pancreatic β-cells were vulnerable to cell damage induced by oxidative stressors including arsenite, due to a muted antioxidant response. Like nuclear factor erythroid 2 like 2 (NFE2L2), NFE2L1 also belongs to the cap 'n' collar (CNC) basic-region leucine zipper (bZIP) transcription factor family, and regulates antioxidant response element (ARE) related genes...
May 23, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28549668/patient-perspectives-on-diabetes-care-across-the-institute-of-medicine-s-six-domains-of-quality
#16
I J Halperin, G Mukerji, M Maione, P Segal, M Wolfs, J Goguen, L Jeffs
OBJECTIVES: To gather patient perspectives on quality of care provided in diabetes clinics within the framework of the Institute of Medicine's 6 domains of quality. METHODS: A qualitative study including semi-structured interviews was conducted at 5 academic hospital sites. Transcripts were analyzed using a direct content approach for themes and subthemes with saturation of themes achieved. Purposive sampling was conducted at 5 diabetes clinics (n=47 interviews)...
May 23, 2017: Canadian Journal of Diabetes
https://www.readbyqxmd.com/read/28549591/single-allele-lmbrd1-knockout-results-in-cardiac-hypertrophy
#17
Linda Tzu-Ling Tseng, Chieh-Liang Lin, Kuei-Hsiang Pan, Kai-Yuan Tzen, Ming-Jai Su, Chia-Ti Tsai, Yi-Han Li, Pai-Chi Li, Fu-Tien Chiang, Shin C Chang, Ming-Fu Chang
BACKGROUND/PURPOSE: LMBD1 protein, a type IV-B plasma membrane protein possessing nine putative trans-membrane domains, was previously demonstrated at cellular level to play a critical part in the signaling cascade of insulin receptor through its involvement in regulating clathrin-mediated endocytosis. However, at physiological level, the significance of LMBD1 protein in cardiac development remains unclear. METHODS: To understand the role of Lmbrd1 gene involved in the cardiac function, heterozygous knockout mice were used as an animal model system...
May 23, 2017: Journal of the Formosan Medical Association, Taiwan Yi Zhi
https://www.readbyqxmd.com/read/28549065/c-elegans-daf-16-foxo-interacts-with-tgf-%C3%A3-bmp-signaling-to-induce-germline-tumor-formation-via-mtorc1-activation
#18
Wenjing Qi, Yijian Yan, Dietmar Pfeifer, Erika Donner V Gromoff, Yimin Wang, Wolfgang Maier, Ralf Baumeister
Activation of the FOXO transcription factor DAF-16 by reduced insulin/IGF signaling (IIS) is considered to be beneficial in C. elegans due to its ability to extend lifespan and to enhance stress resistance. In the germline, cell-autonomous DAF-16 activity prevents stem cell proliferation, thus acting tumor-suppressive. In contrast, hypodermal DAF-16 causes a tumorous germline phenotype characterized by hyperproliferation of the germline stem cells and rupture of the adjacent basement membrane. Here we show that cross-talk between DAF-16 and the transforming growth factor ß (TGFß)/bone morphogenic protein (BMP) signaling pathway causes germline hyperplasia and results in disruption of the basement membrane...
May 26, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28548649/aqueous-humor-endothelin-1-and-total-retinal-blood-flow-in-patients-with-non-proliferative-diabetic-retinopathy
#19
L-A Khuu, F Tayyari, J M Sivak, J G Flanagan, S Singer, M H Brent, D Huang, O Tan, C Hudson
PurposeThe purpose of this study was to determine the association between aqueous ET-1 levels and total retinal blood flow (TRBF) in patients with non-insulin-dependent type 2 diabetes mellitus (T2DM) and early non-proliferative diabetic retinopathy (NPDR).Patients and methodsA total of 15 age-matched controls and 15 T2DM patients with NPDR were recruited into the study. Aqueous humor (~80-120 μl) was collected before cataract surgery to measure the levels of ET-1 using suspension multiplex array technology...
May 26, 2017: Eye
https://www.readbyqxmd.com/read/28548389/night-shift-work-is-associated-with-poorer-glycaemic-control-in-patients-with-type-2-diabetes
#20
Areesa Manodpitipong, Sunee Saetung, Hataikarn Nimitphong, Nantaporn Siwasaranond, Thanawat Wongphan, Chotima Sornsiriwong, Pranee Luckanajantachote, Prasitchai Mangjit, Prasit Keesukphan, Stephanie J Crowley, Megan M Hood, Sirimon Reutrakul
The circadian system plays a role in regulating metabolism. Night-shift work, a form of circadian misalignment, is associated with increased type 2 diabetes risk. This study aimed to determine if night-shift workers with type 2 diabetes experience poorer glycaemic control than non-shift workers. Patients with type 2 diabetes (104 unemployed, 85 day workers and 60 night-shift workers) participated. Sleep duration, sleep quality, morningness-eveningness preference, depressive symptoms and dietary intake were assessed using standardized questionnaires...
May 26, 2017: Journal of Sleep Research
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