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https://www.readbyqxmd.com/read/27912756/mechanisms-of-inflammatory-responses-and-development-of-insulin-resistance-how-are-they-interlinked
#1
Kanwal Rehman, Muhammad Sajid Hamid Akash
BACKGROUND: Insulin resistance (IR) is one of the major hallmark for pathogenesis and etiology of type 2 diabetes mellitus (T2DM). IR is directly interlinked with various inflammatory responses which play crucial role in the development of IR. Inflammatory responses play a crucial role in the pathogenesis and development of IR which is one of the main causative factor for the etiology of T2DM. METHODS: A comprehensive online English literature was searched using various electronic search databases...
December 3, 2016: Journal of Biomedical Science
https://www.readbyqxmd.com/read/27911383/parallel-measurement-of-circadian-clock-gene-expression-and-hormone-secretion-in-human-primary-cell-cultures
#2
Volodymyr Petrenko, Camille Saini, Laurent Perrin, Charna Dibner
Circadian clocks are functional in all light-sensitive organisms, allowing for an adaptation to the external world by anticipating daily environmental changes. Considerable progress in our understanding of the tight connection between the circadian clock and most aspects of physiology has been made in the field over the last decade. However, unraveling the molecular basis that underlies the function of the circadian oscillator in humans stays of highest technical challenge. Here, we provide a detailed description of an experimental approach for long-term (2-5 days) bioluminescence recording and outflow medium collection in cultured human primary cells...
November 11, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27911095/epigenetic-alterations-in-blood-mirror-age-associated-dna-methylation-and-gene-expression-changes-in-human-liver
#3
Madhusudhan Bysani, Alexander Perfilyev, Vanessa D de Mello, Tina Rönn, Emma Nilsson, Jussi Pihlajamäki, Charlotte Ling
AIM: To study the impact of aging on DNA methylation and mRNA expression in human liver. EXPERIMENTAL PROCEDURES: We analysed genome-wide DNA methylation and gene expression in human liver samples using Illumina 450K and HumanHT12 expression BeadChip arrays. RESULTS: DNA methylation analysis of ∼455,000 CpG sites in human liver revealed that age was significantly associated with altered DNA methylation of 20,396 CpG sites. Comparison of liver methylation data with published methylation data in other tissues showed that vast majority of the age-associated significant CpG sites overlapped between liver and blood, whereas a smaller overlap was found between liver and pancreatic islets or adipose tissue, respectively...
December 2, 2016: Epigenomics
https://www.readbyqxmd.com/read/27909715/a-new-scaffold-containing-small-intestinal-submucosa-and-mesenchymal-stem-cells-improves-pancreatic-islet-function-and-survival-in%C3%A2-vitro-and-in%C3%A2-vivo
#4
Dan Wang, Xiaoming Ding, Wujun Xue, Jin Zheng, Xiaohui Tian, Yang Li, Xiaohong Wang, Huanjin Song, Hua Liu, Xiaohui Luo
It is unknown whether a scaffold containing both small intestinal submucosa (SIS) and mesenchymal stem cells (MSCs) for transplantation may improve pancreatic islet function and survival. In this study, we examined the effects of a SIS-MSC scaffold on islet function and survival in vitro and in vivo. MSCs and pancreatic islets were isolated from Sprague-Dawley rats, and SIS was isolated from Bamei pigs. The islets were apportioned among 3 experimental groups as follows: SIS-islets, SIS-MSC-islets and control-islets...
November 29, 2016: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/27905403/infusion-with-human-bone-marrow-derived-mesenchymal-stem-cells-improves-%C3%AE-cell-function-in-patients-and-non-obese-mice-with-severe-diabetes
#5
Lirong Li, Hui Hui, Xiaolei Jia, Jie Zhang, Ying Liu, Qianyue Xu, Dalong Zhu
Mesenchymal stem cells (MSCs) transplantation is a promising therapeutic strategy for type 1 diabetes (T1D). However, little is known on whether MSC transplantation can benefit T1D patients with ketoacidosis and its potential actions. Here, we show that infusion with bone marrow MSCs preserves β-cell function in some T1D patients with ketoacidosis by decreasing exogenous insulin requirement and increasing plasma C-peptide levels up to 1-2 years. MSC transplantation increased plasma and islet insulin contents in non-obese diabetic (NOD) mice with severe diabetes...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27903581/the-plasma-membrane-metal-ion-transporter-zip14-contributes-to-non-transferrin-bound-iron-uptake-by-human-%C3%AE-cells
#6
Richard Coffey, Mitchell D Knutson
The relationship between iron and β cell dysfunction has long been recognized as individuals with iron overload display an increased incidence of diabetes. This link is usually attributed to the accumulation of excess iron in β cells leading to cellular damage and impaired function. Yet, the molecular mechanism(s) by which human β cells take up iron has not been determined. In the present study, we assessed the contribution of the metal-ion transporters ZIP14, ZIP8, and DMT1 to iron uptake by human β cells...
November 30, 2016: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/27903221/in-vitro-generated-mesenchymal-stem-cells-suitable-tools-to-target-insulin-dependent-diabetes-mellitus
#7
Shruti D Dave, Patel C N, Patel J V, Thakkar U G
A synergy of a pre-accumulated genes with an autoimmunity advancing to slow abolition of pancreatic beta-cells causes insulin deficiency and results enrooting insulin dependent diabetes mellitus (IDDM). As per WHO data worldwide about 150 million people are diabetic and the number may rise to more than double by the year 2025. Any absolute cure for IDDM is not available yet, and one of the credible advent in the field include cell-based therapy. At this conjecture, mesenchymal stem cells (MSC) seems to have a specific and beneficial characteristics due to their in vivo as well as in vitro potential to mimic a pancreatic endocrine phenotype and immune-regulatory actions...
November 21, 2016: Current Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/27900263/islet-chrebp-%C3%AE-is-increased-in-diabetes-and-controls-chrebp-%C3%AE-and-glucose-induced-gene-expression-via-a-negative-feedback-loop
#8
Gu Jing, Junqin Chen, Guanlan Xu, Anath Shalev
OBJECTIVE: Carbohydrate-response element-binding protein (ChREBP) is the major transcription factor conferring glucose-induced gene expression in pancreatic islets, liver and adipose tissue. Recently, a novel ChREBP isoform, ChREBP-β, was identified in adipose tissue and found to be also expressed in islets and involved in glucose-induced beta cell proliferation. However, the physiological function of this less abundant β-isoform in the islet, and in diabetes, is largely unknown. The aims of the present study, therefore, were to determine how diabetes affects ChREBP-β and elucidate its physiological role in pancreatic beta cells...
December 2016: Molecular Metabolism
https://www.readbyqxmd.com/read/27899481/hznt8-slc30a8-transgenic-mice-which-overexpress-the-r325w-polymorph-have-reduced-islet-zn2-and-proinsulin-levels-increased-glucose-tolerance-after-a-high-fat-diet-and-altered-levels-of-pancreatic-zinc-binding-proteins
#9
Li Li, Shi Bai, Christian T Sheline
Zinc is involved in both type-1 (T1DM) and type-2 (T2DM) diabetes. The wildtype (WT) form of the beta-cell specific Zn(2+) transporter, ZNT8, is linked to T2DM susceptibility. ZnT8 null mice have a mild phenotype with a slight decrease in glucose tolerance, whereas patients with the ZnT8 R325W polymorphism (rs13266634) have decreased proinsulin staining and susceptibility to T2DM. We measured zinc, insulin, and proinsulin stainings, and IPGTT in transgenic mice overexpressing hZnT8 WT or hZnT8 R325W fed a normal or high fat diet (HFD)...
November 29, 2016: Diabetes
https://www.readbyqxmd.com/read/27899417/emerging-roles-of-glis3-in-neonatal-diabetes-type-1-and-type-2-diabetes
#10
Xianjie Wen, Yisheng Yang
GLI-similar 3 (GLIS3), a member of the Krüppel-like zinc finger protein subfamily, is predominantly expressed in the pancreas, thyroid, and kidney. Glis3 mRNA can be initially detected in mouse pancreas at embryonic day 11.5 and is largely restricted to β cells, pancreatic polypeptide-expressing cells, as well as ductal cells at later stage of pancreas development. Mutations in GLIS3 cause a neonatal diabetes syndrome, characterized by neonatal diabetes, congenital hypothyroidism, and polycystic kidney. Importantly, genome-wide association studies showed that variations of GLIS3 are strongly associated with both type 1 diabetes (T1D) and type 2 diabetes (T2D) in multiple populations...
November 29, 2016: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/27896768/two-dimensional-gel-electrophoresis-of-insulin-secretory-granule-proteins-from-biosynthetically-labeled-pancreatic-islets
#11
Paul C Guest
Pulse-chase radiolabeling of cells with radioactive amino acids is a common method for tracking the biosynthesis of proteins. Radiolabeled newly synthesized proteins can be analyzed by a number of techniques such as two dimensional gel electrophoresis (2DE). This chapter presents a protocol for the biosynthetic labeling of pancreatic islets with (35)S-methionine in the presence of basal and stimulatory concentrations of glucose, followed by subcellular fractionation to produce a secretory granule fraction and analysis of the granule protein contents by 2DE...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27896767/multiplex-sequential-immunoprecipitation-of-insulin-secretory-granule-proteins-from-radiolabeled-pancreatic-islets
#12
Paul C Guest
Pulse radiolabeling of cells with radioactive amino acids is a common method for tracking the biosynthesis of proteins. Specific proteins can then be immunoprecipitated and analyzed by electrophoresis and imaging techniques. This chapter presents a protocol for the biosynthetic labeling of pancreatic islets with (35)S-methionine, followed by multiplex sequential immunoprecipitation of insulin and three other secretory granule accessory proteins. This provided a means of distinguishing those pancreatic islet proteins with different biosynthetic rates in response to the media glucose concentrations...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27895996/label-free-fast-3d-coherent-imaging-reveals-pancreatic-islet-micro-vascularization-and-dynamic-blood-flow
#13
Corinne Berclaz, Daniel Szlag, David Nguyen, Jérôme Extermann, Arno Bouwens, Paul J Marchand, Julia Nilsson, Anja Schmidt-Christensen, Dan Holmberg, Anne Grapin-Botton, Theo Lasser
In diabetes, pancreatic β-cells play a key role. These cells are clustered within structures called islets of Langerhans inside the pancreas and produce insulin, which is directly secreted into the blood stream. The dense vascularization of islets of Langerhans is critical for maintaining a proper regulation of blood glucose homeostasis and is known to be affected from the early stage of diabetes. The deep localization of these islets inside the pancreas in the abdominal cavity renders their in vivo visualization a challenging task...
November 1, 2016: Biomedical Optics Express
https://www.readbyqxmd.com/read/27895821/implanting-1-1b4-human-%C3%AE-cell-pseudoislets-improves-glycaemic-control-in-diabetic-severe-combined-immune-deficient-mice
#14
Alastair D Green, Srividya Vasu, Neville H McClenaghan, Peter R Flatt
AIM: To investigate the potential of implanting pseudoislets formed from human insulin-releasing β-cell lines as an alternative to islet transplantation. METHODS: In this study, the anti-diabetic potential of novel human insulin releasing 1.1B4 β-cells was evaluated by implanting the cells, either as free cell suspensions, or as three-dimensional pseudoislets, into the subscapular region of severe combined immune deficient mice rendered diabetic by single high-dose administration of streptozotocin...
November 15, 2016: World Journal of Diabetes
https://www.readbyqxmd.com/read/27895534/an-automated-perifusion-system-for-modifying-cell-culture-conditions-over-time
#15
Nicholas B Whitticar, Elisha W Strahler, Parthiban Rajan, Savas Kaya, Craig S Nunemaker
BACKGROUND: Cells are continuously exposed to changes in their environment. Endocrine systems, in particular, communicate by rhythms and feedback loops. In this study, we developed an automated system to produce such conditions for cultured cells in a precisely timed manner. We utilized a programmable pair of syringe pumps for inflow and a peristaltic pump for outflow to create rhythmic pulses at 5-min intervals in solutions that mimic the endogenous patterns of insulin produced by pancreatic islets as a test case...
2016: Biological Procedures Online
https://www.readbyqxmd.com/read/27892540/pancreatic-mesenchyme-regulates-islet-cellular-composition-in-a-patched-hedgehog-dependent-manner
#16
Daniel Hibsher, Alona Epshtein, Nufar Oren, Limor Landsman
Pancreas development requires restrained Hedgehog (Hh) signaling activation. While deregulated Hh signaling in the pancreatic mesenchyme has been long suggested to be detrimental for proper organogenesis, this association was not directly shown. Here, we analyzed the contribution of mesenchymal Hh signaling to pancreas development. To increase Hh signaling in the pancreatic mesenchyme of mouse embryos, we deleted Patched1 (Ptch1) in these cells. Our findings indicate that deregulated Hh signaling in mesenchymal cells was sufficient to impair pancreas development, affecting both endocrine and exocrine cells...
November 28, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27889104/three-dimensional-reconstruction-of-the-embryonic-pancreas-in-the-grass-snake-natrix-natrix-l-lepidosauria-serpentes-based-on-histological-studies
#17
Magdalena Kowalska, Mateusz Hermyt, Weronika Rupik
The aim of this study was to evaluate two research hypotheses: H0-the embryonic pancreas in grass snakes develops in the same manner as in all previously investigated amniotes (from three buds) and its topographical localization within the adult body has no relation to its development; H1-the pancreas develops in a different manner and is related to the different topography of internal organs in snakes. For the evaluation of these hypotheses we used histological methods and three-dimensional (3D) reconstructions of the position of the pancreatic buds and surrounding organs at particular developmental stages and of the final position and shape of the pancreatic gland...
November 11, 2016: Zoology: Analysis of Complex Systems, ZACS
https://www.readbyqxmd.com/read/27888197/islet-adaptations-in-fetal-sheep-persist-following-chronic-exposure-to-high-norepinephrine
#18
Xiaochuan Chen, Amy C Kelly, Dustin T Yates, Antoni R Macko, Ronald M Lynch, Sean W Limesand
Complications in pregnancy elevate fetal norepinephrine (NE) concentrations. Previous studies in NE-infused sheep fetuses revealed that sustained exposure to high NE resulted in lower expression of α2-adrenergic receptors in islets and increased insulin secretion responsiveness after acutely terminating the NE infusion. In this study, we determined if the compensatory increase in insulin secretion following chronic elevation of NE is independent of hyperglycemia in sheep fetuses and whether it is persistent in conjunction with islet desensitization to NE...
November 25, 2016: Journal of Endocrinology
https://www.readbyqxmd.com/read/27886258/a-holistic-approach-to-dissecting-sparc-family-protein-complexity-reveals-fstl-1-as-an-inhibitor-of-pancreatic-cancer-cell-growth
#19
Katrina Viloria, Amanda Munasinghe, Sharan Asher, Roberto Bogyere, Lucy Jones, Natasha J Hill
SPARC is a matricellular protein that is involved in both pancreatic cancer and diabetes. It belongs to a wider family of proteins that share structural and functional similarities. Relatively little is known about this extended family, but evidence of regulatory interactions suggests the importance of a holistic approach to their study. We show that Hevin, SPOCKs, and SMOCs are strongly expressed within islets, ducts, and blood vessels, suggesting important roles for these proteins in the normal pancreas, while FSTL-1 expression is localised to the stromal compartment reminiscent of SPARC...
November 25, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27882918/hyperglycaemia-induces-metabolic-dysfunction-and-glycogen-accumulation-in-pancreatic-%C3%AE-cells
#20
Melissa F Brereton, Maria Rohm, Kenju Shimomura, Christian Holland, Sharona Tornovsky-Babeay, Daniela Dadon, Michaela Iberl, Margarita V Chibalina, Sheena Lee, Benjamin Glaser, Yuval Dor, Patrik Rorsman, Anne Clark, Frances M Ashcroft
Insulin secretion from pancreatic β-cells is impaired in all forms of diabetes. The resultant hyperglycaemia has deleterious effects on many tissues, including β-cells. Here we show that chronic hyperglycaemia impairs glucose metabolism and alters expression of metabolic genes in pancreatic islets. In a mouse model of human neonatal diabetes, hyperglycaemia results in marked glycogen accumulation, and increased apoptosis in β-cells. Sulphonylurea therapy rapidly normalizes blood glucose levels, dissipates glycogen stores, increases autophagy and restores β-cell metabolism...
November 24, 2016: Nature Communications
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