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https://www.readbyqxmd.com/read/29777582/comparative-study-of-liraglutide-and-insulin-glargine-on-glycemic-control-and-pancreatic-%C3%AE-cell-function-in-db-db-mice
#1
Yanli Li, Jia Zheng, Yunfeng Shen, Wangen Li, Meimei Liu, Jun Wang, Surong Zhu, Meihua Wu
BACKGROUND The aim of this study was to compare the effects of liraglutide, a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist, and insulin glargine, a long-acting insulin analog, on glycemic control and pancreatic β-cell function in db/db mice. MATERIAL AND METHODS Eight-week-old male db/db mice (n=40) were divided into five groups: the vehicle-treated group (VG) (n=8); the insulin glargine-treated group (GG) (dose, 450 mg/kg) (n=8), the low-dose liraglutide-treated group (LLG) (dose, 75 μg/kg) (n=8), the mid-dose liraglutide-treated group (MLG) (150 μg/kg) (n=8), and the high-dose liraglutide-treated group (HLG) (300 μg/kg) (n=8), treated with subcutaneous injection once daily, from 8-14 weeks-of-age...
May 19, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29726111/clinical-usefulness-of-comprehensive-genetic-screening-in-mody-a-novel-abcc8-mutation-in-a-previously-screened-family
#2
Stephanie Robyn Johnson, Paul Leo, Louise Sonia Conwell, Mark Harris, Matthew Arthur Brown, Emma Letitia Duncan
Maturity-onset diabetes of the young (MODY) is the commonest form of monogenic diabetes, resulting from dominant mutations in one of fourteen genes that regulate beta-cell function (HNF4A, GCK, HNF1A, PDX1, HNF1B, NEUROD1, KLF11, CEL, PAX4, INS, BLK, ABCC8,KCNJ11 and APPL1 1,2 ). MODY accounts for 2-2.5% of childhood diabetes 3 , yet MODY genetic screening is uncommon, even in highly suggestive families, and when performed often limited to the commonest genes (e.g.HNF1A and GCK) 4 .
May 4, 2018: Journal of Diabetes
https://www.readbyqxmd.com/read/29723131/insulin-acts-as-a-repressive-factor-to-inhibit-the-ability-of-par2-to-induce-islet-cell-transdifferentiation
#3
Seung-Hee Lee, Ergeng Hao, David Scharp, Fred Levine
Recently, we showed that pancreatitis in the context of profound β-cell deficiency was sufficient to induce islet cell transdifferentiation. In some circumstances, this effect was sufficient to result in recovery from severe diabetes. More recently, we showed that the molecular mechanism by which pancreatitis induced β-cell neogenesis by transdifferentiation was activation of an atypical GPCR called Protease-Activated Receptor 2 (PAR2). However, the ability of PAR2 to induce transdifferentiation occurred only in the setting of profound β-cell deficiency, implying the existence of a repressive factor from those cells...
May 3, 2018: Islets
https://www.readbyqxmd.com/read/29483633/targeted-mutation-of-ngn3-gene-disrupts-pancreatic-endocrine-cell-development-in-pigs
#4
Timothy P Sheets, Ki-Eun Park, Chi-Hun Park, Steven M Swift, Anne Powell, David M Donovan, Bhanu P Telugu
The domestic pig is an attractive model for biomedical research because of similarities in anatomy and physiology to humans. However, key gaps remain in our understanding of the role of developmental genes in pig, limiting its full potential. In this publication, the role of NEUROGENIN 3 (NGN3), a transcription factor involved in endocrine pancreas development has been investigated by CRISPR/Cas9 gene ablation. Precomplexed Cas9 ribonucleoproteins targeting NGN3 were injected into in vivo derived porcine embryos, and transferred into surrogate females...
February 26, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29449530/the-type-2-diabetes-associated-hmg20a-gene-is-mandatory-for-islet-beta-cell-functional-maturity
#5
Jose M Mellado-Gil, Esther Fuente-Martín, Petra I Lorenzo, Nadia Cobo-Vuilleumier, Livia López-Noriega, Alejandro Martín-Montalvo, Irene de Gracia Herrera Gómez, Maria Ceballos-Chávez, Laura Gómez-Jaramillo, Antonio Campos-Caro, Silvana Y Romero-Zerbo, Júlia Rodríguez-Comas, Joan-Marc Servitja, Gemma Rojo-Martinez, Abdelkrim Hmadcha, Bernat Soria, Marco Bugliani, Piero Marchetti, Francisco J Bérmudez-Silva, Jose C Reyes, Manuel Aguilar-Diosdado, Benoit R Gauthier
HMG20A (also known as iBRAF) is a chromatin factor involved in neuronal differentiation and maturation. Recently small nucleotide polymorphisms (SNPs) in the HMG20A gene have been linked to type 2 diabetes mellitus (T2DM) yet neither expression nor function of this T2DM candidate gene in islets is known. Herein we demonstrate that HMG20A is expressed in both human and mouse islets and that levels are decreased in islets of T2DM donors as compared to islets from non-diabetic donors. In vitro studies in mouse and human islets demonstrated that glucose transiently increased HMG20A transcript levels, a result also observed in islets of gestating mice...
February 15, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29352517/micro-ribonucleic-acid-binding-site-variants-of-type-2-diabetes-candidate-loci-predispose-to-gestational-diabetes-mellitus-in-chinese-han-women
#6
Xiaojing Wang, Wei Li, Liangkun Ma, Fan Ping, Juntao Liu, Xueyan Wu, Jiangfeng Mao, Xi Wang, Min Nie
AIMS/INTRODUCTION: Emerging evidence has suggested that the genetic background of gestational diabetes mellitus (GDM) was analogous to type 2 diabetes mellitus. In contrast to type 2 diabetes mellitus, the genetic studies for GDM were limited. Accordingly, the aim of the present study was to extensively explore the influence of micro-ribonucleic acid-binding single-nucleotide polymorphisms (SNPs) in type 2 diabetes mellitus candidate loci on GDM susceptibility in Chinese. MATERIALS AND METHODS: A total of 839 GDM patients and 900 controls were enrolled...
January 20, 2018: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/29025873/ectopic-expression-of-pax4-in-pancreatic-%C3%AE-cells-results-in-%C3%AE-like-cell-neogenesis
#7
Noémie Druelle, Andhira Vieira, Aidin Shabro, Monica Courtney, Magali Mondin, Samah Rekima, Tiziana Napolitano, Serena Silvano, Sergi Navarro-Sanz, Biljana Hadzic, Fabio Avolio, Minoo Rassoulzadegan, Herbert A Schmid, Ahmed Mansouri, Patrick Collombat
The recent demonstration that pancreatic α cells can be continuously regenerated and converted into β-like cells upon ectopic expression of Pax4 opened new avenues of research in the endocrine cell differentiation and diabetes fields. To determine whether such plasticity was also shared by δ cells, we generated and characterized transgenic animals that express Pax4 specifically in somatostatin-expressing cells. We demonstrate that the ectopic expression of Pax4 in δ cells is sufficient to induce their conversion into functional β-like cells...
December 4, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28837703/combinatorial-effects-of-zinc-deficiency-and-arsenic-exposure-on-zebrafish-danio-rerio-development
#8
Laura M Beaver, Lisa Truong, Carrie L Barton, Tyler T Chase, Greg D Gonnerman, Carmen P Wong, Robert L Tanguay, Emily Ho
Zinc deficiency and chronic low level exposures to inorganic arsenic in drinking water are both significant public health concerns that affect millions of people including pregnant women. These two conditions can co-exist in the human population but little is known about their interaction, and in particular, whether zinc deficiency sensitizes individuals to arsenic exposure and toxicity, especially during critical windows of development. To address this, we utilized the Danio rerio (zebrafish) model to test the hypothesis that parental zinc deficiency sensitizes the developing embryo to low-concentration arsenic toxicity, leading to altered developmental outcomes...
2017: PloS One
https://www.readbyqxmd.com/read/28730907/the-rs10229583-polymorphism-near-paired-box-gene-4-is-associated-with-gestational-diabetes-mellitus-in-chinese-women
#9
Tianyi Xu, Yiru Shi, Jiangbo Liu, Yun Liu, Ailin Zhu, Cui Xie, Yan Zhang, Yan Chen, Lirong Ren
Objective The rs10229583 polymorphism near paired box gene 4 ( PAX4) is associated with insulin resistance and type 2 diabetes. Mutations in the PAX4 gene may be associated with impaired differentiation/development of pancreatic islet beta cells during fetal development and, consequently, a compromised insulin response to high blood glucose. To ascertain whether this polymorphism plays a role in gestational diabetes mellitus (GDM), we investigated the genotypic and allele frequency differences between GDM and normal pregnancies...
January 2018: Journal of International Medical Research
https://www.readbyqxmd.com/read/28701182/do-we-really-need-to-differentiate-mesenchymal-stem-cells-into-insulin-producing-cells-for-attenuation-of-the-autoimmune-responses-in-type-1-diabetes-immunoprophylactic-effects-of-precursors-to-insulin-producing-cells
#10
Anshu Sharma, Rajni Rani
BACKGROUND: Type 1 diabetes (T1D) is a multifactorial autoimmune disorder where pancreatic beta cells are lost before the clinical manifestations of the disease. Administration of mesenchymal stem cells (MSCs) or MSCs differentiated into insulin-producing cells (IPCs) have yielded limited success when used therapeutically. We have evaluated the immunoprophylactic potentials of precursors to insulin-producing cells (pIPCs) and IPCs in nonobese diabetic (NOD) mice to ask a basic question: do we need to differentiate MSCs into IPCs or will pIPCs suffice to attenuate autoimmune responses in T1D? METHODS: Bone marrow-derived MSCs from Balb/c mice were characterized following the International Society for Cellular Therapy (ISCT) guidelines...
July 12, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28665920/lineage-conversion-of-mouse-fibroblasts-to-pancreatic-%C3%AE-cells
#11
Tianjin Liu, Liangliang Sun, Beige Jiang, Limei Li, Jin Cen, Xiaotao Chen, Zhaoyun Zhang, Qinghua Wang, Xin Cheng, Yongquan Shi, Lijian Hui
α-cells, which synthesize glucagon, also support β-cell survival and have the capacity to transdifferentiate into β-cells. However, the role of α-cells in pathological conditions and their putative clinical applications remain elusive due in large part to the lack of mature α-cells. Here, we present a new technique to generate functional α-like cells. α-like cells (iAlpha cells) were generated from mouse fibroblasts by transduction of transcription factors, including Hhex, Foxa3, Gata4, Pdx1 and Pax4, which induce α-cell-specific gene expression and glucagon secretion in response to KCl and Arg stimulation...
June 30, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28657902/induction-of-anti-aging-gene-klotho-with-a-small-chemical-compound-that-demethylates-cpg-islands
#12
Dongju Jung, Yuechi Xu, Zhongjie Sun
Klotho (KL) is described as an anti-aging gene because mutation of Kl gene leads to multiple pre-mature aging phenotypes and shortens lifespan in mice. Growing evidence suggests that an increase in KL expression may be beneficial for age-related diseases such as arteriosclerosis and diabetes. It remains largely unknown, however, how Kl expression could be induced. Here we discovered novel molecular mechanism for induction of Kl expression with a small molecule 'Compound H', N-(2-chlorophenyl)-1H-indole-3-caboxamide...
July 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28597969/the-role-of-epigenetic-regulation-and-pluripotency-related-micrornas-in-differentiation-of-pancreatic-stem-cells-to-beta-cells
#13
Ediz Coskun, Merve Ercin, Selda Gezginci-Oktayoglu
In this study, we aimed to research the effects of class-I HDACs and glucose on differentiation of pancreatic islet derived mesenchymal stem cells (PI-MSCs) to beta cells. Beta cell differentiation determined by flow cytometric analysis and gene expression levels of PDX1, PAX4, PAX6, NKX6.1, NGN3, INS2, and GLUT2. As a result the valproic acid, is an inhibitor of class-I HDACs, caused the highest beta cell differentiation in PI-MSCs. However, the cells in this group were at early stages of differentiation. Glucose co-administration to this group carried the differentiation to higher levels, but these newly formed beta cells were not functional...
January 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28386318/pax4-promotes-pdx1-induced-differentiation-of-mesenchymal-stem-cells-into-insulin-secreting-cells
#14
Lifa Xu, Congjing Xu, Shuping Zhou, Xueke Liu, Jian Wang, Xinkuang Liu, Suping Qian, Yingru Xin, Yi Gao, Yongqiang Zhu, Xiaolong Tang
A shortage of postmortem pancreatic tissue for islet isolation impedes the application of cell replacement therapy in patients with diabetes. As an alternative for islet cell transplantation, transcription factors, including PDX1, PAX4, and neurogenin-3, that aid in the formation of insulin-producing β cells during development have been investigated. The present study evaluated the effects of PAX4 and PDX1 on the differentiation of mesenchymal stem cells (MSCs) into insulin-producing β-like cells in vitro using recombinant adenoviruses carrying PDX1 or PDX1 plus PAX4...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28375156/%C3%AF-3-polyunsaturated-fatty-acids-ameliorate-type-1-diabetes-and-autoimmunity
#15
Xinyun Bi, Fanghong Li, Shanshan Liu, Yan Jin, Xin Zhang, Tao Yang, Yifan Dai, Xiaoxi Li, Allan Zijian Zhao
Despite the benefit of insulin, blockade of autoimmune attack and regeneration of pancreatic islets are ultimate goals for the complete cure of type 1 diabetes (T1D). Long-term consumption of ω-3 polyunsaturated fatty acids (PUFAs) is known to suppress inflammatory processes, making these fatty acids candidates for the prevention and amelioration of autoimmune diseases. Here, we explored the preventative and therapeutic effects of ω-3 PUFAs on T1D. In NOD mice, dietary intervention with ω-3 PUFAs sharply reduced the incidence of T1D, modulated the differentiation of Th cells and Tregs, and decreased the levels of IFN-γ, IL-17, IL-6, and TNF-α...
May 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28282933/the-diabetes-linked-transcription-factor-pax4-from-gene-to-functional-consequences
#16
REVIEW
Petra I Lorenzo, Francisco Juárez-Vicente, Nadia Cobo-Vuilleumier, Mario García-Domínguez, Benoit R Gauthier
Paired box 4 (PAX4) is a key factor in the generation of insulin producing β-cells during embryonic development. In adult islets, PAX4 expression is sequestered to a subset of β-cells that are prone to proliferation and more resistant to stress-induced apoptosis. The importance of this transcription factor for adequate pancreatic islets functionality has been manifested by the association of mutations in PAX4 with the development of diabetes, independently of its etiology. Overexpression of this factor in adult islets stimulates β-cell proliferation and increases their resistance to apoptosis...
March 9, 2017: Genes
https://www.readbyqxmd.com/read/28268202/adverse-effects-of-parental-zinc-deficiency-on-metal-homeostasis-and-embryonic-development-in-a-zebrafish-model
#17
Laura M Beaver, Yasmeen M Nkrumah-Elie, Lisa Truong, Carrie L Barton, Andrea L Knecht, Greg D Gonnerman, Carmen P Wong, Robert L Tanguay, Emily Ho
The high prevalence of zinc deficiency is a global public health concern, and suboptimal maternal zinc consumption has been associated with adverse effects ranging from impaired glucose tolerance to low birthweights. The mechanisms that contribute to altered development and poor health in zinc deficient offspring are not completely understood. To address this gap, we utilized the Danio rerio model and investigated the impact of dietary zinc deficiency on adults and their developing progeny. Zinc deficient adult fish were significantly smaller in size, and had decreases in learning and fitness...
May 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28253300/the-pax-gene-family-highlights-from-cephalopods
#18
Sandra Navet, Auxane Buresi, Sébastien Baratte, Aude Andouche, Laure Bonnaud-Ponticelli, Yann Bassaglia
Pax genes play important roles in Metazoan development. Their evolution has been extensively studied but Lophotrochozoa are usually omitted. We addressed the question of Pax paralog diversity in Lophotrochozoa by a thorough review of available databases. The existence of six Pax families (Pax1/9, Pax2/5/8, Pax3/7, Pax4/6, Paxβ, PoxNeuro) was confirmed and the lophotrochozoan Paxβ subfamily was further characterized. Contrary to the pattern reported in chordates, the Pax2/5/8 family is devoid of homeodomain in Lophotrochozoa...
2017: PloS One
https://www.readbyqxmd.com/read/28096335/myofibril-breakdown-during-atrophy-is-a-delayed-response-requiring-the-transcription-factor-pax4-and-desmin-depolymerization
#19
Alexandra Volodin, Idit Kosti, Alfred Lewis Goldberg, Shenhav Cohen
A hallmark of muscle atrophy is the excessive degradation of myofibrillar proteins primarily by the ubiquitin proteasome system. In mice, during the rapid muscle atrophy induced by fasting, the desmin cytoskeleton and the attached Z-band-bound thin filaments are degraded after ubiquitination by the ubiquitin ligase tripartite motif-containing protein 32 (Trim32). To study the order of events leading to myofibril destruction, we investigated the slower atrophy induced by denervation (disuse). We show that myofibril breakdown is a two-phase process involving the initial disassembly of desmin filaments by Trim32, which leads to the later myofibril breakdown by enzymes, whose expression is increased by the paired box 4 (PAX4) transcription factor...
February 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28090703/differentiation-of-islet-progenitors-regulated-by-nicotinamide-into-transcriptome-verified-%C3%AE-cells-that-ameliorate-diabetes
#20
Fang-Xu Jiang, Kevin Li, Michael Archer, Munish Mehta, Emma Jamieson, Adrian Charles, Jan E Dickinson, Masahito Matsumoto, Grant Morahan
Developmental stage-specific differentiation of stem or progenitor cells into safe and functional cells is of fundamental importance in regenerative medicine, including β-cell replacement. However, the differentiation of islet progenitor cells (IPCs) into insulin-secreting β cells remains elusive. Here, we report that the multifunctional molecule nicotinamide (NIC) is a specific differentiation regulator of mouse IPCs. The differentiated cells regulated by NIC exhibited many characteristics of adult β cells, including ameliorating preclinical diabetes and a highly comparable transcriptome profile...
May 2017: Stem Cells
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