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https://www.readbyqxmd.com/read/29717223/effect-of-the-sodium-glucose-cotransporter-2-inhibitor-luseogliflozin-on-pancreatic-beta-cell-mass-in-db-db-mice-of-different-ages
#1
Kiyohiko Takahashi, Akinobu Nakamura, Hideaki Miyoshi, Hiroshi Nomoto, Naoyuki Kitao, Kazuno Omori, Kohei Yamamoto, Kyu Yong Cho, Yasuo Terauchi, Tatsuya Atsumi
To examine the effects of luseogliflozin, a sodium-glucose cotransporter 2 inhibitor, on pancreatic beta cell mass in db/db mice of different ages. db/db mice aged 6, 10, 14 and 24 weeks old were fed either standard chow (control group) or standard chow containing 0.01% luseogliflozin (luseo group). After 4 weeks, immunohistochemistry and gene expression tests were conducted. In 6-week-old db/db mice, immunohistochemistry revealed a significant increase in beta cell mass in the luseo group compared with the control group after 4 weeks of treatment...
May 1, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29716892/human-proislet-peptide-promotes-pancreatic-progenitor-cells-to-ameliorate-diabetes-via-foxo1-menin-mediated-epigenetic-regulation
#2
Zongzhe Jiang, Diwen Shi, Yifan Tu, Jingjing Tian, Wenjian Zhang, Bowen Xing, Jihua Wang, Suhuan Liu, Jinning Lou, Jan-Åke Gustafsson, Xianxin Hua, Xiaosong Ma
In this study, we investigated how human proislet peptide (HIP) regulates differentiation of human fetus-derived pancreatic progenitor cells (HFPPCs), and explored the potential link between HIP signaling and the menin pathway, a key pathway that regulates differentiation of pancreatic islets. Our data showed that HIP promoted expression of pro-islet transcription factors (TFs) including PDX-1, MAFA and NKX6.1 as well as other maturation markers of β-cells such as insulin, GLUT2, KIR6.2, SUR1 and VDCC. Moreover, HIP increased insulin content, and promoted the ability of HFPPCs to normalize the blood glucose in diabetic mice...
May 1, 2018: Diabetes
https://www.readbyqxmd.com/read/29649104/coordination-of-gpr40-and-ketogenesis-signaling-by-medium-chain-fatty-acids-regulates-beta-cell-function
#3
Julien Benjamin Pujol, Nicolas Christinat, Yann Ratinaud, Claudia Savoia, Siobhan E Mitchell, El Hadji M Dioum
Diabetes prevalence increases with age, and β-cell dysfunction contributes to the incidence of the disease. Dietary lipids have been recognized as contributory factors in the development and progression of the disease. Unlike long chain triglycerides, medium chain triglycerides (MCT) increase fat burning in animal and human subjects as well as serum C-peptide in type 2 diabetes patients. We evaluated the beneficial effects of MCT on β-cells in vivo and in vitro. MCT improved glycemia in aged rats via β-cell function assessed by measuring insulin secretion and content...
April 12, 2018: Nutrients
https://www.readbyqxmd.com/read/29625991/t-3-induces-both-markers-of-maturation-and-aging-in-pancreatic-%C3%AE-cells
#4
Cristina Aguayo-Mazzucato, Terence B Lee, Michelle Matzko, Amanda DiIenno, Habib Rezanejad, Preeti Ramadoss, Thomas Scanlan, Ann Marie Zavacki, P Reed Larsen, Anthony Hollenberg, Clark Colton, Arun Sharma, Susan Bonner-Weir
Previously we showed thyroid hormone (T3 ) enhanced β-cell functional maturation through induction of Mafa High levels of T3 have been linked to decreased lifespan in mammals, and low levels to lengthened lifespan, suggesting a relationship between thyroid hormone and aging. Here we show T3 increased p16 Ink4a (a β-cell senescence marker and effector) mRNA in rodent and human β-cells. The kinetics of Mafa and p16 Ink4a induction suggested both genes as targets of thyroid hormone via TH receptor (THR) binding to specific response elements (TRE)...
April 6, 2018: Diabetes
https://www.readbyqxmd.com/read/29617192/optical-clearing-of-the-pancreas-for-visualization-of-mature-%C3%AE-cells-and-vessels-in-mice
#5
Wataru Nishimura, Asako Sakaue-Sawano, Satoru Takahashi, Atsushi Miyawaki, Kazuki Yasuda, Yasuko Noda
Glucose metabolism is regulated by insulin, which is produced from β-cells in the pancreas. Because insulin is secreted into vessels in response to blood glucose, vascular structures of the pancreas, especially the relationship between vessels and β-cells, are important for physiological and pathological glucose metabolism. Here, we developed a system to visualize vessels surrounding mature β-cells expressing transcription factor MafA in a three-dimensional manner. Optical clearing of the pancreas prevented light scattering of fluorescence driven by the bacterial artificial chromosome (BAC)-mafA promoter in β-cells...
April 4, 2018: Islets
https://www.readbyqxmd.com/read/29605295/heparan-sulfate-in-pancreatic-%C3%AE-cells-contributes-to-normal-glucose-homeostasis-by-regulating-insulin-secretion
#6
Takuro Matsuzawa, Takeo Yoshikawa, Tomomitsu Iida, Anikó Kárpáti, Haruna Kitano, Ryuichi Harada, Tadaho Nakamura, Akira Sugawara, Yu Yamaguchi, Kazuhiko Yanai
Heparan sulfate (HS), a linear polysaccharide, is involved in diverse biological functions of various tissues. HS is expressed in pancreatic β-cells and may be involved in β-cell functions. However, the importance of HS for β-cell function remains unknown. Here, we generated mice with β-cell-specific deletion of Ext1 (βExt1CKO), which encodes an enzyme essential for HS synthesis, to investigate the detailed roles of HS in β-cell function. βExt1CKO mice decreased body weights compared with control mice, despite increased food intake...
March 29, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29590649/circulating-lncrnas-analysis-in-patients-with-type-2-diabetes-reveals-novel-genes-influencing-glucose-metabolism-and-islet-%C3%AE-cell-function
#7
Yuting Ruan, Nie Lin, Qiang Ma, Rongping Chen, Zhen Zhang, Weiheng Wen, Hong Chen, Jia Sun
BACKGROUND/AIMS: The islet is an important endocrine organ to secrete insulin to regulate the metabolism of glucose and maintain the stability of blood glucose. Long noncoding RNAs (lncRNAs) are involved in a variety of biological functions and play key roles in many diseases, including type 2 diabetes (T2D). The aim of this study was to determine whether lncRNA-p3134 is associated with glucose metabolism and insulin signaling in pancreatic β cells. METHODS: LncRNA microarray technology was used to identify the differentially expressed circulating lncRNAs in T2D patients...
2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29550076/long-term-correction-of-diabetes-in-mice-by-in-vivo-reprogramming-of-pancreatic-ducts
#8
Yuhan Wang, Craig Dorrell, Willscott E Naugler, Michael Heskett, Paul Spellman, Bin Li, Feorillo Galivo, Annelise Haft, Leslie Wakefield, Markus Grompe
Direct lineage reprogramming can convert readily available cells in the body into desired cell types for cell replacement therapy. This is usually achieved through forced activation or repression of lineage-defining factors or pathways. In particular, reprogramming toward the pancreatic β cell fate has been of great interest in the search for new diabetes therapies. It has been suggested that cells from various endodermal lineages can be converted to β-like cells. However, it is unclear how closely induced cells resemble endogenous pancreatic β cells and whether different cell types have the same reprogramming potential...
February 21, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29542001/rna-seq-analysis-of-islets-to-characterise-the-dedifferentiation-in-type-2-diabetes-model-mice-db-db
#9
Abraham Neelankal John, Ramesh Ram, Fang-Xu Jiang
Type 2 diabetes (T2D) is a global health issue and dedifferentiation plays underlying causes in the pathophysiology of T2D; however, there is a lack of understanding in the mechanism. Dedifferentiation results from the loss of function of pancreatic β-cells alongside a reduction in essential transcription factors under various physiological stressors. Our study aimed to establish db/db as an animal model for dedifferentiation by using RNA sequencing to compare the gene expression profile in islets isolated from wild-type, db/+ and db/db mice, and qPCR was performed to validate those significant genes...
March 14, 2018: Endocrine Pathology
https://www.readbyqxmd.com/read/29529600/long-noncoding-rna-meg3-regulates-mafa-expression-in-mouse-beta-cells-by-inactivating-rad21-smc3-or-sin3%C3%AE
#10
Ning Wang, Yanan Zhu, Min Xie, Lintao Wang, Feiyan Jin, Yihui Li, Qingxin Yuan, Wei De
BACKGROUND/AIMS: The main pathogenic mechanism of diabetes is a decrease in the number of islet beta cells or a decline in their function. Recent studies have shown that pancreatic long noncoding RNAs (lncRNAs) have a high degree of tissue specificity and may be involved in the maintenance of islet cells function and the development of diabetes. The aim of this study was to investigate the molecular regulatory mechanism of mouse maternal expressed gene 3 (Meg3) in insulin biosynthesis in pancreatic islets...
2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29511614/the-combined-effect-of-pdx1-overexpression-and-shh-manipulation-on-the-function-of-insulin-producing-cells-derived-from-adipose-tissue-stem-cells
#11
Mahmoud Hashemi Tabar, Mohammad Reza Tabandeh, Eskandar Moghimipour, Dian Dayer, Ata A Ghadiri, Elham Allah Bakhshi, Mahmoud Orazizadeh, Mohammad Ali Ghafari
Pancreatic and duodenal homeobox 1 (Pdx1) and Sonic hedgehog (Shh) are the key regulators of beta-cell function. In vitro experiments have shown that there is significant cooperation between Pdx1 and Shh with regard to the production and maintenance of insulin-producing cells (IPCs). In this study, the combined effect of Pdx1 overexpression and Shh manipulation on the function of adipose tissue-derived IPCs was determined. A eukaryotic expression vector ( Pdx1- pCDNA3.1(+)) was constructed and transfected into a Chinese hamster ovary (CHO) cell line...
March 2018: FEBS Open Bio
https://www.readbyqxmd.com/read/29503087/functional-beta-cell-mass-from-device-encapsulated-hesc-derived-pancreatic-endoderm-achieving-metabolic-control
#12
Thomas Robert, Ines De Mesmaeker, Geert M Stangé, Krista G Suenens, Zhidong Ling, Evert J Kroon, Daniel G Pipeleers
Human stem cells represent a potential source for implants that replace the depleted functional beta cell mass (FBM) in diabetes patients. Human embryonic stem cell-derived pancreatic endoderm (hES-PE) can generate implants with glucose-responsive beta cells capable of reducing hyperglycemia in mice. This study with device-encapsulated hES-PE (4 × 106 cells/mouse) determines the biologic characteristics at which implants establish metabolic control during a 50-week follow-up. A metabolically adequate FBM was achieved by (1) formation of a sufficient beta cell number (>0...
March 13, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/29453918/high-dose-of-histone-deacetylase-inhibitors-affects-insulin-secretory-mechanism-of-pancreatic-beta-cell-line
#13
Eiji Yamato
OBJECTIVE: Histone deacytylase inhibitors (HDACis) inhibit the deacetylation of the lysine residue of proteins, including histones, and regulate the transcription of a variety of genes. Recently, HDACis have been used clinically as anti-cancer drugs and possible anti-diabetic drugs. Even though HDACis have been proven to protect the cytokine-induced damage of pancreatic beta cells, evidence also shows that high doses of HDACis are cytotoxic. In the present study, we, therefore, investigated the eff ect of HDACis on insulin secretion in a pancreatic beta cell line...
January 1, 2018: Endocrine Regulations
https://www.readbyqxmd.com/read/29449530/the-type-2-diabetes-associated-hmg20a-gene-is-mandatory-for-islet-beta-cell-functional-maturity
#14
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/29428671/swertisin-ameliorates-diabetes-by-triggering-pancreatic-progenitors-for-islet-neogenesis-in-streptozotocin-treated-balb-c-mice
#15
Abhay Srivastava, Nidheesh Dadheech, Mitul Vakani, Sarita Gupta
In the present study, Swertisin's role in triggering resident pancreatic progenitors for islet neogenesis in Streptozotocin (STZ) diabetic mice was explored. STZ diabetic mice when treated with Swertisin demonstrated reversion to normoglycemia and significant elevation of fasting serum insulin levels. On screening the pancreatic tissue post Swertisin treatment in the STZ diabetic mice, we observed significant up-regulation of key transcription factors viz. Pdx1, Neurog3, MafA and Nkx6.1 required for islet neogenesis and beta cell homeostasis...
April 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29422234/an-overview-of-type-2-diabetes-and-importance-of-vitamin-d3-vitamin-d-receptor-interaction-in-pancreatic-%C3%AE-cells
#16
REVIEW
Abraham Neelankal John, Fang-Xu Jiang
One significant health issue that plagues contemporary society is that of Type 2 diabetes (T2D). This disease is characterised by higher-than-average blood glucose levels as a result of a combination of insulin resistance and insufficient insulin secretions from the β-cells of pancreatic islets of Langerhans. Previous developmental research into the pancreas has identified how early precursor genes of pancreatic β-cells, such as Cpal, Ngn3, NeuroD, Ptf1a, and cMyc, play an essential role in the differentiation of these cells...
April 2018: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/29351489/cooperative-function-of-pdx1-and-oc1-in-multipotent-pancreatic-progenitors-impacts-postnatal-islet-maturation-and-adaptability
#17
Peter A Kropp, Jennifer C Dunn, Bethany A Carboneau, Doris A Stoffers, Maureen Gannon
The transcription factors pancreatic and duodenal homeobox 1 (Pdx1) and onecut1 (Oc1) are coexpressed in multipotent pancreatic progenitors (MPCs), but their expression patterns diverge in hormone-expressing cells, with Oc1 expression being extinguished in the endocrine lineage and Pdx1 being maintained at high levels in β-cells. We previously demonstrated that cooperative function of these two factors in MPCs is necessary for proper specification and differentiation of pancreatic endocrine cells. In those studies, we observed a persistent decrease in expression of the β-cell maturity factor MafA...
April 1, 2018: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29348175/glucose-regulates-mafa-transcription-factor-abundance-and-insulin-gene-expression-by-inhibiting-amp-activated-protein-kinase-in-pancreatic-%C3%AE-cells
#18
Ryo Iwaoka, Kohsuke Kataoka
Insulin mRNA expression in pancreatic islet β-cells is up-regulated by extracellular glucose concentration, but the underlying mechanism remains incompletely understood. MafA is a transcriptional activator specifically enriched in β-cells that binds to the insulin gene promoter. Its expression is transcriptionally and posttranscriptionally regulated by glucose. Moreover, AMP-activated protein kinase (AMPK), a regulator of cellular energy homeostasis, is inhibited by high glucose, and this inhibition is essential for the up-regulation of insulin gene expression and glucose-stimulated insulin secretion (GSIS)...
March 9, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29339498/-mafa-missense-mutation-causes-familial-insulinomatosis-and-diabetes-mellitus
#19
Donato Iacovazzo, Sarah E Flanagan, Emily Walker, Rosana Quezado, Fernando Antonio de Sousa Barros, Richard Caswell, Matthew B Johnson, Matthew Wakeling, Michael Brändle, Min Guo, Mary N Dang, Plamena Gabrovska, Bruno Niederle, Emanuel Christ, Stefan Jenni, Bence Sipos, Maike Nieser, Andrea Frilling, Ketan Dhatariya, Philippe Chanson, Wouter W de Herder, Björn Konukiewitz, Günter Klöppel, Roland Stein, Márta Korbonits, Sian Ellard
The β-cell-enriched MAFA transcription factor plays a central role in regulating glucose-stimulated insulin secretion while also demonstrating oncogenic transformation potential in vitro. No disease-causing MAFA variants have been previously described. We investigated a large pedigree with autosomal dominant inheritance of diabetes mellitus or insulinomatosis, an adult-onset condition of recurrent hyperinsulinemic hypoglycemia caused by multiple insulin-secreting neuroendocrine tumors of the pancreas. Using exome sequencing, we identified a missense MAFA mutation (p...
January 30, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29324782/mafb-is-dispensable-for-the-fetal-testis-morphogenesis-and-the-maintenance-of-spermatogenesis-in-adult-mice
#20
Hossam H Shawki, Hisashi Oishi, Toshiaki Usui, Yu Kitadate, Walaa A Basha, Ahmed M Abdellatif, Kazunori Hasegawa, Risa Okada, Keiji Mochida, Hany A El-Shemy, Masafumi Muratani, Atsuo Ogura, Shosei Yoshida, Satoru Takahashi
The transcription factor MAFB is an important regulator of the development and differentiation of various organs and tissues. Previous studies have shown that MAFB is expressed in embryonic and adult mouse testes and is expected to act as the downstream target of retinoic acid (RA) to initiate spermatogenesis. However, its exact localization and function remain unclear. Here, we localized MAFB expression in embryonic and adult testes and analyzed its gene function using Mafb-deficient mice. We found that MAFB and c-MAF are the only large MAF transcription factors expressed in testes, while MAFA and NRL are not...
2018: PloS One
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