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https://www.readbyqxmd.com/read/28942790/glucagon-like-peptide-1-receptor-agonists-a-class-update-for-treating-type-2-diabetes
#1
REVIEW
Julie A Lovshin
Current management options for treating type 2 diabetes are diverse. Many different classes of antidiabetes therapies are used in clinic, and several new candidates are in late-phase clinical trial. This therapeutic abundance is a windfall for patients because it facilitates individualized patient care. Evidence-based positioning of these agents is challenging, however, requiring comprehensive and balanced familiarity with each drug class. In this review, I provide a clinical update of glucagon-like peptide-1 receptor agonists (GLP-1RAs), a class of incretin-based, injectable antidiabetes therapies which improve fasting and postprandial blood glucose control through glucose-dependent pancreatic islet cell hormone secretion without significant risks for hypoglycemia...
October 2017: Canadian Journal of Diabetes
https://www.readbyqxmd.com/read/28941594/fenofibrate-attenuates-fatty-acid-induced-islet-%C3%AE-cell-dysfunction-and-apoptosis-via-inhibiting-the-nf-%C3%AE%C2%BAb-mif-dependent-inflammatory-pathway
#2
Shuang Zheng, Xingxing Ren, Tingting Han, Yawen Chen, Huiying Qiu, Wei Liu, Yaomin Hu
BACKGROUND: Fatty acid-induced lipotoxicity and macrophage migration inhibitory factor (MIF) affect pancreatic β-cell function, and may promote the development of diabetes mellitus. However, the association of lipotoxicity with MIF and the effect of Fenofibrate on β-cell function remain unknown. METHODS: LPL+/- mice and MIN6 cells stimulated with palmitic acid (PA) were utilized as models of lipid metabolism disorders. Factors associated with insulin secretion and apoptosis were assessed in the presence or absence of Fenofibrate...
September 20, 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/28941330/purity-of-islet-preparations-and-5-year-metabolic-outcome-of-allogenic-islet-transplantation
#3
K Benomar, M Chetboun, S Espiard, A Jannin, K Le Mapihan, V Gmyr, R Caiazzo, F Torres, V Raverdy, C Bonner, D'Herbomez, P Pigny, C Noel, J Kerr-Conte, F Pattou, M C Vantyghem
In allogenic islet transplantation (IT), high purity of islet preparations and low contamination by non-islet cells are generally favored. The aim of the present study was to analyze the relation between the purity of transplanted preparations, and graft function during 5 years post-IT. Twenty-four type 1 diabetic patients, followed-up 5 years after IT, were enrolled. Metabolic parameters and daily insulin requirements were compared between patients who received islet preparations with a mean purity < 50% (LOW purity) or ≥50% (HIGH purity)...
September 23, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28940946/islet-neuropeptide-y-receptors-are-functionally-conserved-and-novel-targets-for-the-preservation-of-beta-cell-mass
#4
Z J Franklin, A Tsakmaki, P Fonseca Pedro, A J King, G C Huang, S J Persaud, G A Bewick
OBJECTIVE: Two unmet therapeutic strategies for diabetes treatment are prevention of beta-cell death and stimulation of beta-cell replication. Our aim was to characterise the role of Neuropeptide Y receptors in the control of beta-cell mass. METHODS: We used endogenous and selective agonists of the NPY receptor system to explore its role in the prevention of beta-cell apoptosis and proliferation in islets isolated from both mouse and human donors. We further explored the intra-cellular signalling cascades involved using chemical inhibitors of key signalling pathways...
September 22, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28939870/different-developmental-histories-of-beta-cells-generate-functional-and-proliferative-heterogeneity-during-islet-growth
#5
Sumeet Pal Singh, Sharan Janjuha, Theresa Hartmann, Özge Kayisoglu, Judith Konantz, Sarah Birke, Priyanka Murawala, Ezzaldin Ahmed Alfar, Kei Murata, Anne Eugster, Naoki Tsuji, Edward R Morrissey, Michael Brand, Nikolay Ninov
The proliferative and functional heterogeneity among seemingly uniform cells is a universal phenomenon. Identifying the underlying factors requires single-cell analysis of function and proliferation. Here we show that the pancreatic beta-cells in zebrafish exhibit different growth-promoting and functional properties, which in part reflect differences in the time elapsed since birth of the cells. Calcium imaging shows that the beta-cells in the embryonic islet become functional during early zebrafish development...
September 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/28938514/-2-4-fluorobenzamido-4-methylthiazole-5-carboxylic-acid-a-novel-thiazole-compound-ameliorates-insulin-sensitivity-and-hyperlipidaemia-in-streptozotocin-induced-diabetic-rats-plausible-role-of-inflammatory-and-oxidative-stress-markers
#6
Yam Nath Paudel, Md Rahmat Ali, Mohammad Adil, Sandhya Bawa, Manju Sharma
Emerging evidence suggests that thiazole compounds are of great interest due to their protective effect against DM. Protective effects of thiazole derivatives against hyperglycemia have been demonstrated in earlier in vitro and in vivo studies. Previously, anti-oxidant and free radical scavenging activities of 2-(4-Fluorobenzamido)-4-methylthiazole-5-carboxylicacid, a newly developed thiazole derivative (NDTD), have been well-documented. Current study investigated the pharmacological effect of NDTD on hyperglycaemia, insulin sensitivity, lipid profile, anti-inflammatory and oxidative stress markers in an animal model...
September 18, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28938487/regulation-of-endogenous-male-rodent-glp-1-secretion-and-human-islet-insulin-secretion-by-antagonism-of-somatostatin-receptor-5
#7
Thomas B Farb, Marta Adeva, Thomas J Beauchamp, Over Cabrera, David A Coates, Tamika DeShea Meredith, Brian A Droz, Alexander Efanov, James V Ficorilli, Susan L Gackenheimer, Maria A Martinez-Grau, Victoriano Molero, Gema Ruano, Michael A Statnick, Todd M Suter, Samreen K Syed, Miguel A Toledo, Francis S Willard, Xin Zhou, Krister B Bokvist, David G Barrett
Incretin and insulin responses to nutrient loads are suppressed in persons with diabetes, resulting in decreased glycemic control. Whereas agents including sulfonylureas and Dipeptidyl peptidase-4 inhibitors (DPP4i) partially reverse these effects and provide therapeutic benefit, their modes of action limit efficacy. Because somatostatin (SST) has been shown to suppress both insulin and GLP-1 secretion through the Gi-coupled SST receptor 5 (SSTR5) isoform in vitro, antagonism of SSTR5 may improve glycemic control via intervention in both pathways...
September 11, 2017: Endocrinology
https://www.readbyqxmd.com/read/28938442/angiotensin-ii-causes-beta-cell-dysfunction-through-an-er-stress-induced-pro-inflammatory-response
#8
Stanley M H Chan, Yeh-Siang Lau, Alyson A Miller, Jacqueline M Ku, Simon Potocnik, Ji-Ming Ye, Owen L Woodman, Terence P Herbert
The metabolic syndrome is associated with an increase in the activation of renin angiotensin system (RAS) and inhibition of RAS reduces the incidence of new onset diabetes. Importantly, angiotensin II (AngII), independently of its vasoconstrictor action causes beta-cell inflammation and dysfunction, which may be an early step in the development of type-2 diabetes. The aim of this study was to determine how AngII causes beta cell dysfunction. Islets of Langerhans were isolated from C57BL/6J mice that had been infused with AngII in the presence or absence of taurine-conjugated ursodeoxycholic acid (TUDCA) and effects on ER stress, inflammation and beta cell function determined...
August 17, 2017: Endocrinology
https://www.readbyqxmd.com/read/28938426/a-sustained-activation-of-pancreatic-nmdars-is-a-novel-factor-of-%C3%AE-cell-apoptosis-and-dysfunction
#9
Xiao-Ting Huang, Shao-Jie Yue, Chen Li, Yan-Hong Huang, Qing-Mei Cheng, Xiao-Hong Li, Cai-Xia Hao, Ling-Zhi Wang, Jian-Ping Xu, Ming Ji, Chen Chen, Dan-Dan Feng, Zi-Qiang Luo
Type 2 diabetes, which features β-cell failure, is caused by the decrease of β-cell mass and insulin secretory function. Current treatments fail to halt the decrease of functional β-cell mass. Strategies to prevent β-cell apoptosis and dysfunction are highly desirable. Recently, our group and others have reported that blockade of N-methyl-D-aspartate receptors (NMDARs) in the islets has been proposed to prevent the progress of type 2 diabetes through improving β-cell function. It suggests that a sustained activation of the NMDARs may exhibit deleterious effect on β-cells...
September 4, 2017: Endocrinology
https://www.readbyqxmd.com/read/28938416/pancreatic-histopathology-of-human-monogenic-diabetes-due-to-causal-variants-in-kcnj11-hnf1a-gata6-and-lmna
#10
May Sanyoura, Laura Jacobsen, David Carmody, Daniela Del Gaudio, Gorka Alkorta-Aranburu, Kelly Arndt, Ying Ying Hu, Frances Kobiernicki, Irina Kusmartseva, Mark A Atkinson, Louis H Philipson, Desmond Schatz, Martha Campbell-Thompson, Siri Atma W Greeley
Context: Monogenic diabetes is thought to account for 2% of all diabetes cases but most patients are misdiagnosed as type 1 or type 2 diabetes. To date, little is known about the histopathological features of pancreases from patients with monogenic diabetes. Objective: Retrospective study of the JDRF Network for Pancreatic Organ donors with Diabetes biorepository was used to identify possible cases with monogenic diabetes and to compare effects of genetic variants on pancreas histology...
August 16, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28938414/sex-and-tissue-specific-role-of-estrogen-sulfotransferase-in-energy-homeostasis-and-insulin-sensitivity
#11
Wojciech G Garbacz, Mengxi Jiang, Meishu Xu, Jun Yamauchi, H Henry Dong, Wen Xie
Estrogen Sulfotransferase (EST) catalyzes the sulfoconjugation and deactivation of estrogens. Previously we showed that loss of Est in male ob/ob mice, but not in female ob/ob mice, exacerbated the diabetic phenotype, but the underlying mechanism was unclear. Here we show that transgenic reconstitution of Est in the adipose tissue, but not in the liver, attenuated diabetic phenotype in Est deficient ob/ob mice (obe). Mechanistically, adipose reconstitution of Est in obe mice (oae) resulted in reduced local and systemic inflammation, improved insulin sensitivity, and increased energy expenditure...
September 5, 2017: Endocrinology
https://www.readbyqxmd.com/read/28937406/tolerance-in-xenotransplantation
#12
Kazuhiko Yamada, Megan Sykes, David H Sachs
PURPOSE OF REVIEW: This review describes recent progress in tolerance-inducing strategies across xenogeneic immunological barriers as well as the potential benefit of a tolerance strategy for islets and kidney xenotransplantation. RECENT FINDINGS: Using advanced gene editing technologies, xenotransplantation from multitransgenic alpha-1,3-galactosyltransferase knockout pigs has demonstrated marked prolongation of renal xenograft survival, ranging from days to greater than several months for life-supporting kidneys, and more than 2 years in a heterotopic nonlife-supporting cardiac xenograft model...
September 20, 2017: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/28937262/empirical-factors-affecting-the-quality-of-non-negative-matrix-factorization-of-mammalian-cell-raman-spectra
#13
H Georg Schulze, Stanislav O Konorov, James M Piret, Michael W Blades, Robin F B Turner
Mammalian cells contain various macromolecules that can be investigated non-invasively with Raman spectroscopy. The particular mixture of major macromolecules present in a cell being probed are reflected in the measured Raman spectra. Determining macromolecular identities and estimating their concentrations from these mixture Raman spectra can distinguish cell types and otherwise enable biological research. However, the application of canonical multivariate methods, such as principal component analysis (PCA), to perform spectral unmixing yields mathematical solutions that can be difficult to interpret...
January 1, 2017: Applied Spectroscopy
https://www.readbyqxmd.com/read/28935144/effects-of-dietary-biotin-supplementation-on-glucagon-production-secretion-and-action
#14
Maria-Luisa Lazo-de-la-Vega-Monroy, Elena Larrieta, Wilma Tixi-Verdugo, Rafael Ramírez-Mondragón, Ileana Hernández-Araiza, Michael S German, Cristina Fernandez-Mejia
OBJECTIVE: Despite increasing evidence that pharmacologic concentrations of biotin modify glucose metabolism, to our knowledge there have not been any studies addressing the effects of biotin supplementation on glucagon production and secretion, considering glucagon is one of the major hormones in maintaining glucose homeostasis. The aim of this study was to investigate the effects of dietary biotin supplementation on glucagon expression, secretion, and action. METHODS: Male BALB/cAnN Hsd mice were fed a control or a biotin-supplemented diet (1...
November 2017: Nutrition
https://www.readbyqxmd.com/read/28934349/the-association-between-acute-graft-versus-host-disease-and-antimicrobial-peptide-expression-in-the-gastrointestinal-tract-after-allogeneic-stem-cell-transplantation
#15
Daniela Weber, Katrin Frauenschläger, Sakhila Ghimire, Katrin Peter, Isabella Panzer, Andreas Hiergeist, Markus Weber, Daniel Kutny, Daniel Wolff, Matthias Grube, Elisabeth Huber, Peter Oefner, Andre Gessner, Thomas Hehlgans, Wolfgang Herr, Ernst Holler
Intestinal microbiota disruption is associated with acute gastrointestinal (GI) Graft-versus-Host Disease (GvHD) and poor outcome after allogeneic stem cell transplantation (ASCT). Here, in a retrospective analysis of 200 patients undergoing ASCT at the Regensburg University Medical Center, we assessed the relative expression of Paneth cell antimicrobial peptides (AMPs), Human Defensins (HD) 5 and 6 and regenerating islet-derived 3α (Reg3α), in 292 human intestinal biopsies as well as Reg3α serum levels in relation to acute GI GvHD...
2017: PloS One
https://www.readbyqxmd.com/read/28934293/generation-of-a-pancreatic-cancer-model-using-a-pdx1-flp-recombinase-knock-in-allele
#16
Jinghai Wu, Xin Liu, Sunayana G Nayak, Jason R Pitarresi, Maria C Cuitiño, Lianbo Yu, Blake E Hildreth, Katie A Thies, Daniel J Schilling, Soledad A Fernandez, Gustavo Leone, Michael C Ostrowski
The contribution of the tumor microenvironment to the development of pancreatic adenocarcinoma (PDAC) is unclear. The LSL-KrasG12D/+;LSL-p53R172H/+;Pdx-1-Cre (KPC) tumor model, which is widely utilized to faithfully recapitulate human pancreatic cancer, depends on Cre-mediated recombination in the epithelial lineage to drive tumorigenesis. Therefore, specific Cre-loxP recombination in stromal cells cannot be applied in this model, limiting the in vivo investigation of stromal genetics in tumor initiation and progression...
2017: PloS One
https://www.readbyqxmd.com/read/28933628/effectiveness-of-different-molecular-forms-of-c-histolyticum-class-i-collagenase-to-recover-islets
#17
Michael L Green, Andrew G Breite, Caleb A Beechler, Francis E Dwulet, Robert C McCarthy
One factor that may contribute to variability between different lots of purified collagenase to recover islets is the molecular form of C. histolyticum class I (C1) collagenase used in the isolation procedure. Two different enzyme mixtures containing C1, class II (C2) collagenase and BP Protease were compared for their effectiveness to recover islets from split adult porcine pancreas. The same enzyme activities per g trimmed tissue were used for all isolations with the only difference being the mass of C1 required to achieve 25,000 collagen degradation activity U/g tissue...
September 21, 2017: Islets
https://www.readbyqxmd.com/read/28932650/gene-editing-gene-therapy-and-cell-xenotransplantation-cell-transplantation-across-species
#18
REVIEW
Nizar I Mourad, Pierre Gianello
PURPOSE OF REVIEW: Cell xenotransplantation has the potential to provide a safe, ethically acceptable, unlimited source for cell replacement therapies. This review focuses on genetic modification strategies aimed to overcome remaining hurdles standing in the way of clinical porcine islet transplantation and to develop neural cell xenotransplantation. RECENT FINDINGS: In addition to previously described genetic modifications aimed to mitigate hyperacute rejection, instant blood-mediated inflammatory reaction, and cell-mediated rejection, new data showing the possibility of increasing porcine islet insulin secretion by transgenesis is an interesting addition to the array of genetically modified pigs available for xenotransplantation...
2017: Current Transplantation Reports
https://www.readbyqxmd.com/read/28931935/alpha-tc1-and-beta-tc-6-genomic-profiling-uncovers-both-shared-and-distinct-transcriptional-regulatory-features-with-their-primary-islet-counterparts
#19
Nathan Lawlor, Ahrim Youn, Romy Kursawe, Duygu Ucar, Michael L Stitzel
Alpha TC1 (αTC1) and Beta-TC-6 (βTC6) mouse islet cell lines are cellular models of islet (dys)function and type 2 diabetes (T2D). However, genomic characteristics of these cells, and their similarities to primary islet alpha and beta cells, are undefined. Here, we report the epigenomic (ATAC-seq) and transcriptomic (RNA-seq) landscapes of αTC1 and βTC6 cells. Each cell type exhibits hallmarks of its primary islet cell counterpart including cell-specific expression of beta (e.g., Pdx1) and alpha (e.g., Arx) cell transcription factors (TFs), and enrichment of binding motifs for these TFs in αTC1/βTC6 cis-regulatory elements...
September 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28931557/protective-effect-of-cyanidin-3-o-glucoside-on-neonatal-porcine-islets
#20
Chao Li, Bin Yang, Zhihao Xu, Eric Boivin, Mazzen Black, Wenlong Huang, Baoyou Xu, Ping Wu, Bo Zhang, Xian Li, Kunsong Chen, Yulian Wu, Gina Rayat
Oxidative stress is a major cause of islet injury and dysfunction during isolation and transplantation procedures. Cyanidin-3-O-glucoside (C3G), which is present in various fruits and vegetables especially in Chinese bayberry, shows potent antioxidant property. In this study, we determined whether C3G could protect neonatal porcine islets (NPI) from reactive oxygen species (H2O2)-induced injury in vitro and promote the function of NPI in diabetic mice. We found that C3G had no deleterious effect on NPI and that C3G protected NPI from damage induced by H2O2...
September 20, 2017: Journal of Endocrinology
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