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https://www.readbyqxmd.com/read/28924486/expression-of-transcription-factors-in-men1-associated-pancreatic-neuroendocrine-tumors
#1
Yasutaka Takeda, Yukihiro Fujita, Kentaro Sakai, Tomoe Abe, Tomonobu Nakamura, Tsuyoshi Yanagimachi, Hidemitsu Sakagami, Jun Honjo, Atsuko Abiko, Yuichi Makino, Masakazu Haneda
MEN1-associated pancreatic neuroendocrine tumors (pNETs) may potentially express distinct hormones, but the mechanism has not been elucidated. Transcription factors such as MafA and Pdx1 have been identified to lead to beta cell differentiation, while Arx and Brn4 to alpha cell differentiation in developing pancreas. We hypothesized those transcription factors are important to produce specific hormones in pNETs, similarly to developing pancreas, and examined the expression of transcription factors in a case of MEN1 who showed immunohistological coexistence of several hormone-producing pNETs including insulinoma...
2017: Endocrinology, Diabetes & Metabolism Case Reports
https://www.readbyqxmd.com/read/28922976/transient-impairment-of-islet-architectural-development-in-pancreas-specific-bmpr1a-deleted-prenatal-mice-involves-reduced-expression-of-e-cadherin
#2
Fang-Xu Jiang, Leonard Charles Harrison
Bone morphogenetic protein (BMP) signaling plays critical roles on the development of a large array of embryonic organs and promotes the in vitro formation of pancreatic cystoid colonies containing insulin-producing cells. However, this signaling and its underlying mechanism on in vivo development of prenatal pancreas have not been clearly understood. To address these questions, we analyzed with a variety of techniques the prenatal mouse pancreas after Pdx1 (the pancreas and duodenal homeobox factor 1 gene)-driving deletion of the BMP receptor type 1a gene (Bmpr1a)...
September 19, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28919426/improving-glycemic-control-in-model-mice-with-type-2-diabetes-by-increasing-superoxide-dismutase-sod-activity-using-silk-fibroin-hydrolysate-sfh
#3
Harry Jung, Yoo Yeon Kim, Boyoung Kim, Hajin Nam, Jun Gyo Suh
Islet cell dysfunction in type 2 diabetes is primarily attributed to the increased apoptosis of pancreatic beta cells. Silk fibroin hydrolysate (SFH) has an effect on blood in type 2 diabetes model mice (C57BL/KsJ-db/db). However, its exact mechanism is unknown. The type 2 diabetes model mice were randomly divided into non-diabetic mice (ND), diabetic mice (DB), and diabetic mice treated with silk fibroin hydrolysate (DB-SFH). The results showed that SFH significantly decreased fasting blood glucose and hemoglobin A1c (HbA1c)...
September 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28919305/magnolol-protects-pancreatic-%C3%AE-cells-against-methylglyoxal-induced-cellular-dysfunction
#4
Kwang Sik Suh, Suk Chon, Woon-Won Jung, Eun Mi Choi
Chronic hyperglycemia aggravates insulin resistance, in part due to increased formation of advanced glycation end-products (AGEs). Methylglyoxal (MG), a major precursor of AGEs, accumulates abnormally in various tissues and organs and participates in oxidative damage. We investigated the insulinotropic benefits of magnolol, a hydroxylated biphenyl compound isolated from Magnolia officinalis, in pancreatic β-cells exposed to MG in vitro. When exposed to cytotoxic levels of MG for 48 h, RIN-m5F β-cells exhibited a significant loss of viability and impaired insulin secretion, whereas pretreatment with magnolol protected against MG-induced cell death and decreased insulin secretion...
September 15, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28918929/vitamin-d-receptor-targeted-treatment-to-prevent-pathological-dedifferentiation-of-pancreatic-%C3%AE-cells-under-hyperglycaemic-stress
#5
A Neelankal John, Z Iqbal, S Colley, G Morahan, M Makishima, F-X Jiang
Dedifferentiation has been identified as one of the causes of β-cell failure resulting in type 2 diabetes (T2D). This study tested whether increasing vitamin D receptor (VDR) expression prevents dedifferentiation of β cells in a high-glucose state in vitro. Culturing a mouse insulinoma cell line (MIN6) in a high-glucose environment decreased VDR expression. However, increased VDR following vitamin D3 (VD3) treatment improved insulin release of early-passage MIN6 and insulin index of db/- (heterozygous) islets to levels seen in normal functional islets...
September 11, 2017: Diabetes & Metabolism
https://www.readbyqxmd.com/read/28883507/organotypic-pancreatoids-with-native-mesenchyme-develop-insulin-producing-endocrine-cells
#6
Marissa A Scavuzzo, Diane Yang, Malgorzata Borowiak
Replacement of lost beta cells in patients with diabetes has the potential to alleviate them of their disease, yet current protocols to make beta cells are inadequate for therapy. In vitro screens can reveal the signals necessary for endocrine maturation to improve beta cell production, however the complexities of in vivo development that lead to beta cell formation are lost in two-dimensional systems. Here, we create three-dimensional organotypic pancreatic cultures, named pancreatoids, composed of embryonic day 10...
September 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28874671/crispr-cas9-mediated-one-step-disabling-of-pancreatogenesis-in-pigs
#7
Jun Wu, Marcela Vilarino, Keiichiro Suzuki, Daiji Okamura, Yanina Soledad Bogliotti, Insung Park, Joan Rowe, Bret McNabb, Pablo Juan Ross, Juan Carlos Izpisua Belmonte
Genome editing using programmable nucleases has revolutionized biomedical research. CRISPR-Cas9 mediated zygote genome editing enables high efficient production of knockout animals suitable for studying development and relevant human diseases. Here we report efficient disabling pancreatogenesis in pig embryos via zygotic co-delivery of Cas9 mRNA and dual sgRNAs targeting the PDX1 gene, which when combined with chimeric-competent human pluriopotent stem cells may serve as a suitable platform for the xeno-generation of human tissues and organs in pigs...
September 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28873332/use-of-rgd-functionalized-sandwich-cultures-to-promote-redifferentiation-of-human-pancreatic-beta-cells-after-in-vitro-expansion
#8
Caterina Aloy-Reverté, José L Moreno-Amador, Montserrat Nacher, Eduard Montanya, Carlos E Semino
Islet transplantation has provided proof of concept that cell therapy can restore normoglycemia in patients with diabetes. However, limited availability of islet tissue severely restricts the clinical use of the treatment. Thus, there is an urgent need to develop new strategies to generate an abundant source of insulin-producing cells that could be used to treat diabetes. A potential approach is the in vitro expansion of pancreatic beta cells obtained from cadaveric organ donors. However, when human beta cells are expanded in vitro, they dedifferentiate and lose the expression of insulin, probably as a consequence of pancreatic islet dissociation into single cells...
August 31, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28864900/expression-of-master-regulatory-genes-of-embryonic-development-in-pancreatic-tumors
#9
L G Kondratyeva, I P Chernov, M V Zinovyeva, E P Kopantzev, E D Sverdlov
The expression level of some important master regulators of embryonic development of the pancreas in the tumor samples of this human organ was determined. We found that the transcription of SOX9, GATA4, PDX1, PTF1a, and HNF1b genes in the tumor samples was reduced as compared to the samples of normal pancreatic tissues, and the KLF5 gene expression in the tumor cells was elevated. We assume that all the studied genes, except KLF5, form a single regulatory module that supports the identity of tumor progenitor cells...
July 2017: Doklady. Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28864896/dependence-of-expression-of-regulatory-master-genes-of-embryonic-development-in-pancreatic-cancer-cells-on-the-intracellular-concentration-of-the-master-regulator-pdx1
#10
L G Kondratyeva, D A Didych, I P Chernov, E P Kopantzev, E A Stukacheva, T V Vinogradova, E D Sverdlov
Exogenous expression of the gene encoding the pancreatic master regulator PDX1 in cell lines with different degrees of differentiation of pancreatic cancer cells is accompanied by changes in the expression of known master genes involved in cancer progression. In BxPC3(PDX+) cells, as compared to BxPC3(PDX-), we detected an increased expression of the following genes: NKX6.1 (2 times), NR5A2 (2.5 times), KLF5 (1.8 times), ZEB1 (3 times), and ONECUT1 (1.3 times), as well as a decreased expression of MUC1 and SLUG genes (3 and 2 times, respectively)...
July 2017: Doklady. Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28843156/small-molecule-at7867-proliferates-pdx1-expressing-pancreatic-progenitor-cells-derived-from-human-pluripotent-stem-cells
#11
Azuma Kimura, Taro Toyoda, Yohei Nishi, Makoto Nasu, Akira Ohta, Kenji Osafune
While pancreatic islet transplantation achieves insulin independence in type 1 diabetes (T1D) patients, its widespread application is limited by donor tissue scarcity. Pancreatic progenitor cells (PPCs) give rise to all cell types in the pancreas during development. PPCs derived from human pluripotent stem cells have been shown to differentiate into functional β cells both in vitro and in vivo, and to reverse hyperglycemia, at least in mice. Therefore, PPCs have great potential to serve as an alternative cell source for cell therapy, and the identification of compounds that facilitate PPC proliferation could provide stable and large-scale pancreatic cell preparation systems in clinical settings...
August 17, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28842933/plasma-stem-cell-factor-levels-are-associated-with-risk-of-cardiovascular-disease-and-death
#12
Harry Björkbacka, Ingrid Yao Mattisson, Maria Wigren, Olle Melander, Gunilla Nordin Fredrikson, Eva Bengtsson, Isabel Gonçalves, Peter Almgren, Jens O Lagerstedt, Marju Orho-Melander, Gunnar Engström, Jan Nilsson
OBJECTIVE: Stem cell factor (SCF) is a key growth factor for several types of stem and progenitor cells. There is experimental evidence that such cells are of importance for maintaining the integrity of the cardiovascular system. We investigated the association between circulating levels of SCF and risk for development of cardiovascular events and death. METHODS: SCF was analyzed by the Proximity Extension Assay technique in plasma from 4742 subjects participating in the Malmö Diet and Cancer Study...
August 26, 2017: Journal of Internal Medicine
https://www.readbyqxmd.com/read/28836148/anti-diabetic-actions-of-esculentin-2cha-1-30-and-its-stable-analogues-in-a-diet-induced-model-of-obesity-diabetes
#13
Srividya Vasu, Opeolu O Ojo, R Charlotte Moffett, J Michael Conlon, Peter R Flatt, Yasser H A Abdel-Wahab
Actions of esculentin-2CHa(1-30) (GFSSIFRGVAKFASKGLGKDLAKLGVDLVA) and its analogues, ([D-Arg(7), D-Lys(15), D-Lys(23)]-esculentin-2CHa(1-30) and [Lys(15)-octanoate]-esculentin-2CHa(1-30), were evaluated in high-fat fed NIH Swiss mice with impaired glucose tolerance and insulin resistance. Twice-daily i.p. administration of the esculentin-2CHa(1-30) peptides (75 nmol/kg body weight) or exendin-4 (25 nmol/kg) for 28 days reduced body weight, without altering cumulative energy intake. All peptides reduced blood glucose levels by 6-12 mmol/l concomitant with lower plasma insulin levels, with significance evident from day 6...
August 23, 2017: Amino Acids
https://www.readbyqxmd.com/read/28835709/glycoprotein-2-is-a-specific-cell-surface-marker-of-human-pancreatic-progenitors
#14
Kathryn F Cogger, Ankit Sinha, Farida Sarangi, Emily C McGaugh, Diane Saunders, Craig Dorrell, Salvador Mejia-Guerrero, Yasaman Aghazadeh, Jillian L Rourke, Robert A Screaton, Markus Grompe, Philip R Streeter, Alvin C Powers, Marcela Brissova, Thomas Kislinger, M Cristina Nostro
PDX1(+)/NKX6-1(+) pancreatic progenitors (PPs) give rise to endocrine cells both in vitro and in vivo. This cell population can be successfully differentiated from human pluripotent stem cells (hPSCs) and hold the potential to generate an unlimited supply of β cells for diabetes treatment. However, the efficiency of PP generation in vitro is highly variable, negatively impacting reproducibility and validation of in vitro and in vivo studies, and consequently, translation to the clinic. Here, we report the use of a proteomics approach to phenotypically characterize hPSC-derived PPs and distinguish these cells from non-PP populations during differentiation...
August 24, 2017: Nature Communications
https://www.readbyqxmd.com/read/28813430/reprogramming-human-gallbladder-cells-into-insulin-producing-%C3%AE-like-cells
#15
Feorillo Galivo, Eric Benedetti, Yuhan Wang, Carl Pelz, Jonathan Schug, Klaus H Kaestner, Markus Grompe
The gallbladder and cystic duct (GBCs) are parts of the extrahepatic biliary tree and share a common developmental origin with the ventral pancreas. Here, we report on the very first genetic reprogramming of patient-derived human GBCs to β-like cells for potential autologous cell replacement therapy for type 1 diabetes. We developed a robust method for large-scale expansion of human GBCs ex vivo. GBCs were reprogrammed into insulin-producing pancreatic β-like cells by a combined adenoviral-mediated expression of hallmark pancreatic endocrine transcription factors PDX1, MAFA, NEUROG3, and PAX6 and differentiation culture in vitro...
2017: PloS One
https://www.readbyqxmd.com/read/28793244/rho-associated-kinases-and-non-muscle-myosin-iis-inhibit-the-differentiation-of-human-ipscs-to-pancreatic-endoderm
#16
Taro Toyoda, Azuma Kimura, Hiromi Tanaka, Tomonaga Ameku, Atsushi Mima, Yurie Hirose, Masahiro Nakamura, Akira Watanabe, Kenji Osafune
There has been increasing success with the generation of pancreatic cells from human induced pluripotent stem cells (hiPSCs); however, the molecular mechanisms of the differentiation remain elusive. The purpose of this study was to reveal novel molecular mechanisms for differentiation to PDX1(+)NKX6.1(+) pancreatic endoderm cells, which are pancreatic committed progenitor cells. PDX1(+) posterior foregut cells differentiated from hiPSCs failed to differentiate into pancreatic endoderm cells at low cell density, but Rho-associated kinase (ROCK) or non-muscle myosin II (NM II) inhibitors rescued the differentiation potential...
August 8, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28790184/adiponectin-protects-against-development-of-metabolic-disturbances-in-a-pcos-mouse-model
#17
Anna Benrick, Belén Chanclón, Peter Micallef, Yanling Wu, Laila Hadi, John M Shelton, Elisabet Stener-Victorin, Ingrid Wernstedt Asterholm
Adiponectin, together with adipocyte size, is the strongest factor associated with insulin resistance in women with polycystic ovary syndrome (PCOS). This study investigates the causal relationship between adiponectin levels and metabolic and reproductive functions in PCOS. Prepubertal mice overexpressing adiponectin from adipose tissue (APNtg), adiponectin knockouts (APNko), and their wild-type (WT) littermate mice were continuously exposed to placebo or dihydrotestosterone (DHT) to induce PCOS-like traits...
August 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28774890/mir-338-controls-bpa-triggered-pancreatic-islets-insulin-secretory-dysfunction-from-compensation-to-decompensation-by-targeting-pdx-1
#18
Jie Wei, Dongxiao Ding, Tao Wang, Qiong Liu, Yi Lin
Bisphenol A (BPA) can disrupt glucose homeostasis and impair pancreatic islet function; however, the mechanisms behind these effects are poorly understood. Male mice (4 wk old) were treated with BPA (50 or 500 μg/kg/day) for 8 wk. Whole-body glucose homeostasis, pancreatic islet morphology and function, and miR-338-mediated molecular signal transduction analyses were examined. We showed that BPA treatment led to a disruption of glucose tolerance and a compensatory increase of pancreatic islets insulin secretion and pancreatic and duodenal homeobox 1 (Pdx1) expression in mice...
August 3, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28765528/pdx1-cre-driven-conditional-gene-depletion-suggests-pak4-as-dispensable-for-mouse-pancreas-development
#19
Miao Zhao, Parisa Rabieifar, Tânia D F Costa, Ting Zhuang, Audrey Minden, Matthias Löhr, Rainer Heuchel, Staffan Strömblad
Constitutive depletion of p21-activated kinase 4 (PAK4) in the mouse causes embryonic lethality associated with heart and brain defects. Given that conventional gene depletion of PAK1 or PAK3 caused functional deficits in the mouse pancreas, while gene depletion of PAK5 or PAK6 did not, we asked if PAK4 might have a functional role in pancreas development. We therefore introduced conditional, Pdx1-Cre-mediated, pancreatic PAK4 gene depletion in the mouse, verified by loss of PAK4 protein expression in the pancreas...
August 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28765173/a2a-adenosine-receptors-control-pancreatic-dysfunction-in-high-fat-diet-induced-obesity
#20
Balázs Csóka, Gábor Törő, Joana Vindeirinho, Zoltán V Varga, Balázs Koscsó, Zoltán H Németh, Endre Kókai, Luca Antonioli, Mara Suleiman, Piero Marchetti, Karolina Cseri, Ádám Deák, László Virág, Pál Pacher, Péter Bai, György Haskó
Adenosine, a key extracellular signaling mediator, regulates several aspects of metabolism by activating 4 G protein-coupled receptors, the A1, A2A, A2B, and A3 adenosine receptors (ARs). The role of A2AARs in regulating high-fat-diet (HFD)-induced metabolic derangements is unknown. To evaluate the role of A2AARs in regulating glucose and insulin homeostasis in obesity, we fed A2AAR knockout (KO) and control mice an HFD for 16 wk to initiate HFD-induced metabolic disorder. We found that genetic deletion of A2AARs caused impaired glucose tolerance in mice fed an HFD...
August 1, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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