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https://www.readbyqxmd.com/read/28238527/interferon-alpha-impairs-insulin-production-in-human-beta-cells-via-endoplasmic-reticulum-stress
#1
Angela Lombardi, Yaron Tomer
Despite substantial advances in the research exploring the pathogenesis of Type 1 Diabetes (T1D), the pathophysiological mechanisms involved remain unknown. We hypothesized in this study that interferon alpha (IFNα) participates in the early stages of T1D development by triggering endoplasmic reticulum (ER) stress. To verify our hypothesis, human islets and human EndoC-βH1 cells were exposed to IFNα and tested for ER stress markers, glucose stimulated insulin secretion (GSIS) and insulin content. IFNα treatment induced upregulation of ER stress markers including Binding immunoglobulin Protein, phospho-eukaryotic translation initiation factor 2α, spliced- X-box binding protein-1, C/EBP homologous protein and activating transcription factor 4...
February 23, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28237718/endogenous-beta-cell-cart-regulates-insulin-secretion-and-transcription-of-beta-cell-genes
#2
L Shcherbina, A Edlund, J L S Esguerra, M Abels, Y Zhou, E Ottosson-Laakso, C B Wollheim, O Hansson, L Eliasson, N Wierup
Impaired beta-cell function is key to the development of type 2 diabetes. Cocaine- and amphetamine-regulated transcript (CART) is an islet peptide with insulinotropic and glucagonostatic properties. Here we studied the role of endogenous CART in beta-cell function. CART silencing in INS-1 (832/13) beta-cells reduced insulin secretion and production, ATP levels and beta-cell exocytosis. This was substantiated by reduced expression of several exocytosis genes, as well as reduced expression of genes important for insulin secretion and processing...
February 22, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28230643/mtor-inhibition-clinical-transplantation-pancreas-islet
#3
Thierry Berney, Axel Andres, Christian Toso, Pietro Majno, Jean-Paul Squifflet
This brief overview discusses the beneficial and deleterious effects of mTOR inhibitors on beta-cells, and how sirolimus- and everolimus-based immunosuppression have impacted on practices and outcomes of pancreas and islet transplantation. Sirolimus was the cornerstone of immunosuppressive regimens in islet transplantation at the turn of the millenium, but utilization of mTOR inhibitors has progressively decreased from >80% to <50% of islet transplant recipients in more recent years. For whole pancreas transplantation, mTOR inhibitors were used in approximately 20% of patients in the early 2000s, but this dropped over the years to <10% currently...
February 23, 2017: Transplantation
https://www.readbyqxmd.com/read/28228865/identification-of-beta-cell-dysfunction-at-the-pre-symptomatic-stage-of-diabetes-mellitus-by-novel-analytical-system-liquid-biopsy-measurements-in-femtograms
#4
REVIEW
Kurt Krapfenbauer
BACKGROUND: Diabetes mellitus is produced and progresses as a consequence of complex and gradual processes, in which a variety of alterations of the endocrine pancreas, are involved and which mainly result in beta cell failure. Those molecular alterations can be found in the bloodstream, which suggests that we could quantify specific biomarkers in plasma or serum by very sensitive methods before the onset diabetes mellitus is diagnosed. However, classical methods of protein analysis such as electrophoresis, Western blot, ELISA, and liquid chromatography are generally time-consuming, lab-intensive, and not sensitive enough to detect such alteration in a pre-symptomatic state of the disease...
December 2017: EPMA Journal
https://www.readbyqxmd.com/read/28222755/wd-repeat-protein-wdr13-is-a-novel-transcriptional-regulator-of-c-jun-and-modulates-intestinal-homeostasis-in-mice
#5
Vijay Pratap Singh, Saritha Katta, Satish Kumar
BACKGROUND: WDR13 is a member of the WD repeat protein family and is expressed in several tissues of human and mice. Previous studies in our laboratory showed that the lack of this gene in mice resulted in mild obesity, hyperinsulinemia, enhanced beta cell proliferation and protection from inflammation. However, the molecular mechanism of WDR13 action is not well understood. METHODS: In the present study, we used AOM/DSS to induce colitis-mediated colorectal tumor after establishing expression of Wdr13 gene in colon...
February 21, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28217528/how-many-oral-antidiabetic-drugs-before-insulin
#6
Jayant Kelwade, Harsh Parekh, Vaibhav Dukle, Bipin Kumar Sethi
Worsening of glycemic control in type 2 Diabetes mellitus occur on account of declining beta cell function. This calls for up titration of the chosen drug, addition of another agent with complementary action and eventually insulin usually after 2 or three OADs. Introduction of insulin has many issues which include parenteral route of administration, cost and enhancement of hypoglycemic tendency. We propose the addition of another OAD in lieu of insulin in whom glycemic control can be achieved equally well without insulin...
January 2017: Indian Journal of Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28216051/morin-activates-the-nrf2-are-pathway-and-reduces-oxidative-stress-induced-dna-damage-in-pancreatic-beta-cells
#7
Pachamuthu Vanitha, S Senthil Kumar, Sireesh Dornadula, S Anantha Kumar, Palanisamy Rajaguru, Kunka Mohanram Ramkumar
Oxidative stress is an important factor contributing to the pathogenesis of diabetes and its complications. In our earlier study, we demonstrated the antidiabetic efficacy of morin by regulating key enzymes of carbohydrate metabolism in diabetic rats. The present study was designed to assess the antigenotoxic potential of morin in pancreatic β-cells, using the COMET assay. To explore its potential mechanisms of action, three genotoxic agents, H2O2 which induces DNA damage by the generation of reactive oxygen species, streptozotocin (STZ) by RNS and Methyl methanesulfonate (MMS) by DNA alkylation was used...
February 16, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28213757/germinal-centre-frequency-is-decreased-in-pancreatic-lymph-nodes-from-individuals-with-recent-onset-type-1-diabetes
#8
Abby Willcox, Sarah J Richardson, Lucy S K Walker, Sally C Kent, Noel G Morgan, Kathleen M Gillespie
AIMS/HYPOTHESIS: Pancreatic lymph nodes (PLNs) are critical sites for the initial interaction between islet autoantigens and autoreactive lymphocytes, but the histology of PLNs in tissue from individuals with type 1 diabetes has not been analysed in detail. The aim of this study was to examine PLN tissue sections from healthy donors compared with those at risk of, or with recent-onset and longer-duration type 1 diabetes. METHODS: Immunofluorescence staining was used to examine PLN sections from the following donor groups: non-diabetic (n=15), non-diabetic islet autoantibody-positive (n=5), recent-onset (≤1...
February 17, 2017: Diabetologia
https://www.readbyqxmd.com/read/28213644/circulating-micrornas-and-diabetes-mellitus-a-novel-tool-for-disease-prediction-diagnosis-and-staging
#9
REVIEW
G Sebastiani, L Nigi, G E Grieco, F Mancarella, G Ventriglia, F Dotta
Diabetes is a complex, multifactorial group of metabolic diseases characterized by chronic hyperglycaemia due to pancreatic beta-cell dysfunction and/or loss. It is characterized by an asymptomatic and highly variable prodromic phase, which renders diabetes mellitus difficult to be predicted with sufficient accuracy. Despite several efforts in the identification and standardization of newly trustable. Biomarkers able to predict and follow-up diabetes and to specifically subtype its different forms, few of them have proven of clinical utility...
February 17, 2017: Journal of Endocrinological Investigation
https://www.readbyqxmd.com/read/28212332/type-1-diabetes-candidate-genes-linked-to-pancreatic-islet-cell-inflammation-and-beta-cell-apoptosis
#10
REVIEW
Joachim Størling, Flemming Pociot
Type 1 diabetes (T1D) is a chronic immune-mediated disease resulting from the selective destruction of the insulin-producing pancreatic islet β-cells. Susceptibility to the disease is the result of complex interactions between environmental and genetic risk factors. Genome-wide association studies (GWAS) have identified more than 50 genetic regions that affect the risk of developing T1D. Most of these susceptibility loci, however, harbor several genes, and the causal variant(s) and gene(s) for most of the loci remain to be established...
February 16, 2017: Genes
https://www.readbyqxmd.com/read/28202581/identification-and-functional-implications-of-sodium-myo-inositol-cotransporter-1-in-pancreatic-beta-cells-and-type-2-diabetes-mellitus
#11
Stephen Yu Ting Li, Sam Tsz Wai Cheng, Dan Zhang, Po Sing Leung
Myo-inositol (MI), the precursor of the second messenger phosphoinositide (PI), mediates multiple cellular events. Rat islets exhibit active transport of MI, though the mechanism involved remains elusive. Here, we report, for the first time, the expression of sodium/myo-inositol cotransporter 1 (SMIT1) in rat islets and specifically, β-cells. Genetic or pharmacological inhibition of SMIT impaired glucose-stimulated insulin secretion by INS-1E cells, probably via down-regulation of PI signaling. Additionally, we found that SMIT1 expression in INS-1E cells and isolated islets was augmented by acute high-glucose exposure and reduced in chronic hyperglycemia conditions...
February 15, 2017: Diabetes
https://www.readbyqxmd.com/read/28198081/latent-autoimmune-diabetes-in-adults-lada-in-asian-and-european-populations
#12
REVIEW
Alok Kumar, Alberto de Leiva
Diabetes Mellitus (DM) is a chronic disorder caused by relative or absolute insulin deficiency and characterized by chronic hyperglycaemia. It is expected that by year 2025, 80% of all Type 2 Diabetic patients will be living in developing or low and middle income countries. Among Asians, there has been an overall increase in abdominal obesity however, the risk of diabetes in these populations starts at much lower body mass index (BMI) as compared to Caucasians. A significant proportion of diabetic patients with adult-onset, initially non-requiring insulin treatment, depicts diabetes-associated autoantibodies in their sera...
February 14, 2017: Diabetes/metabolism Research and Reviews
https://www.readbyqxmd.com/read/28193789/enriching-islet-phospholipids-with-eicosapentaenoic-acid-reduces-prostaglandin-e2-signaling-and-enhances-diabetic-%C3%AE-cell-function
#13
Joshua C Neuman, Michael D Schaid, Allison L Brill, Rachel J Fenske, Carly R Kibbe, Danielle A Fontaine, Sophia M Sdao, Harpreet K Brar, Kelsey M Connors, Haley N Wienkes, Kevin W Eliceiri, Matthew J Merrins, Dawn B Davis, Michelle E Kimple
Prostaglandin E2 (PGE2) is derived from arachidonic acid, while PGE3 is derived from eicosapentaenoic acid (EPA) using the same downstream metabolic enzymes. Little is known about the impact of EPA and PGE3 on β-cell function, particularly in the diabetic state. In this work, we determined PGE3 elicits a 10-fold weaker reduction in glucose-stimulated insulin secretion through the EP3 receptor as compared to PGE2 We tested the hypothesis that enriching pancreatic islet cell membranes with EPA, thereby reducing arachidonic acid abundance, would positively impact β-cell function in the diabetic state...
February 13, 2017: Diabetes
https://www.readbyqxmd.com/read/28193492/characterization-of-acyl-coa-synthetase-isoforms-in-pancreatic-beta-cells-gene-silencing-shows-participation-of-acsl3-and-acsl4-in-insulin-secretion
#14
Israr-Ul H Ansari, Melissa J Longacre, Scott W Stoker, Mindy A Kendrick, Lucas M O'Neill, Laura J Zitur, Luis A Fernandez, James M Ntambi, Michael J MacDonald
Long-chain acyl-CoA synthetases (ACSLs) convert fatty acids to fatty acyl-CoAs to regulate various physiologic processes. We characterized the ACSL isoforms in a cell line of homogeneous rat beta cells (INS-1 832/13 cells) and human pancreatic islets. ACSL4 and ACSL3 proteins were present in the beta cells and human and rat pancreatic islets and concentrated in insulin secretory granules and less in mitochondria and negligible in other intracellular organelles. ACSL1 and ACSL6 proteins were not seen in INS-1 832/13 cells or pancreatic islets...
February 11, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28191333/effects-of-fish-oil-supplementation-on-gestational-diabetes-mellitus-gdm-a-systematic-review
#15
REVIEW
Alireza Ostadrahimi, Sakineh Mohammad-Alizadeh, Mozhgan Mirgafourvand, Sina Yaghoubi, Elham Shahrisa, Azizeh Farshbaf-Khalili
CONTEXT: One of the most common complications of pregnancy is gestational diabetes mellitus (GDM), which is increasing worldwide. Experimental and epidemiological studies have shown that higher intake of n-3 long-chain polyunsaturated fatty acids may decrease the risk of various diseases such as diabetes. The objective of this study was to assess the effect of fish oil supplementation on the prevention and treatment of GDM. EVIDENCE ACQUISITION: This systematic review was performed by searching several databases, including PubMed, Scopus, Google Scholar, the Cochrane Library, ProQuest, Science Direct SID, Magiran and IranMedex since 1983...
November 2016: Iranian Red Crescent Medical Journal
https://www.readbyqxmd.com/read/28182280/anti-prediabetic-effect-of-rose-hip-rosa-canina-extract-in-spontaneously-diabetic-torii-rats
#16
Si Jing Chen, Chiwa Aikawa, Risa Yoshida, Tomoaki Kawaguchi, Toshiro Matsui
BACKGROUND: Prediabetes, a high-risk state for developing diabetes showing impaired glucose tolerance but normal fasting blood glucose level, has increasing prevalence worldwide. However, no study to prevent impaired glucose tolerance at prediabetic stage by anti-diabetic functional foods has been reported. Thus, the aim of the present study was to evaluate the anti-prediabetic effect of rose hip in a prediabetic rat model. RESULTS: Spontaneously Diabetic Torii (SDT) rats were supplemented with hot-water extract of rose hip at a dose of 100 mg/kg body weight/day for 12 weeks...
February 9, 2017: Journal of the Science of Food and Agriculture
https://www.readbyqxmd.com/read/28181104/apigenin-attenuates-streptozotocin-induced-pancreatic-%C3%AE-cell-damage-by-its-protective-effects-on-cellular-antioxidant-defense
#17
Ning Wang, Wen Jing Yi, Lu Tan, Jia Hui Zhang, Jiamin Xu, Yi Chen, Mengting Qin, Shuang Yu, Jing Guan, Rui Zhang
Pancreatic beta cells are very sensitive to oxidative stress, which is one of the major causes of cell damages in diabetes. Growing interest has focused on the development of effective therapeutics to protect pancreatic cells from oxidative stress and searching for potentially protective antioxidants for treating diabetes. Apigenin, a plant-derived flavonoid, was investigated to determine whether it could protect rat insulinoma cell lines (RINm5F pancreatic beta cells) against streptozotocin (STZ)-induced oxidative damages and the mechanisms implicated...
February 8, 2017: In Vitro Cellular & Developmental Biology. Animal
https://www.readbyqxmd.com/read/28179377/hepcidin-links-gluco-toxicity-to-pancreatic-beta-cell-dysfunction-through-inhibiting-pdx-1-expression
#18
Xuhua Mao, Hucheng Chen, Junmin Tang, Liangliang Wang, Tingting Shu
OBJECTIVE: Gluco-toxicity is a term used to convey the detrimental effect of hyperglycemia on β-cell function through impaired insulin synthesis. Although it is known that the expression and activity of several key insulin transcription regulators is inhibited, other molecular mechanisms that mediate gluco-toxicity are poorly defined. Our objective was to explore the role of hepcidin in β-cell gluco-toxicity. DESIGN: We first confirmed that high glucose levels inhibited hepcidin expression in the mouse insulinoma cell line, MIN6...
February 8, 2017: Endocrine Connections
https://www.readbyqxmd.com/read/28174593/glucose-driven-changes-in-beta-cell-identity-are-important-for-function-and-possibly-autoimmune-vulnerability-during-the-progression-of-type-1-diabetes
#19
Gordon C Weir, Susan Bonner-Weir
This commentary explores the hypothesis that when autoimmunity leads to a fall of beta cell mass during the progression of type 1 diabetes (T1D), rising glucose levels cause major changes in beta cell identity. This then leads to profound changes in secretory function and less well-understood changes in beta cell susceptibility to autoimmune destruction, which may influence of rate of progression of beta cell killing.
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/28174291/local-sphingosine-kinase-1-activity-improves-islet-transplantation
#20
Darling Rojas-Canales, Daniella Penko, Kay K Myo Min, Kate A Parham, Heshan Peiris, Rainer V Haberberger, Stuart M Pitson, Chris Drogemuller, Damien J Keating, Shane T Grey, Patrick T Coates, Claudine S Bonder, Claire F Jessup
Pancreatic islet transplantation is a promising clinical treatment for type I diabetes (T1D), but success is limited by extensive beta cell death in the immediate post-transplant period, and impaired islet function in the longer term. Following transplantation, appropriate vascular remodelling is crucial to ensure the survival and function of engrafted islets. The sphingosine kinase pathway is an important regulator of vascular beds, but its role in the survival and function of transplanted islets is unknown...
February 7, 2017: Diabetes
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