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https://www.readbyqxmd.com/read/28938442/angiotensin-ii-causes-beta-cell-dysfunction-through-an-er-stress-induced-pro-inflammatory-response
#1
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/28938416/pancreatic-histopathology-of-human-monogenic-diabetes-due-to-causal-variants-in-kcnj11-hnf1a-gata6-and-lmna
#2
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/28936587/metabolite-ratios-as-potential-biomarkers-for-type-2-diabetes-a-direct-study
#3
Sophie Molnos, Simone Wahl, Mark Haid, E Marelise W Eekhoff, René Pool, Anna Floegel, Joris Deelen, Daniela Much, Cornelia Prehn, Michaela Breier, Harmen H Draisma, Nienke van Leeuwen, Annemarie M C Simonis-Bik, Anna Jonsson, Gonneke Willemsen, Wolfgang Bernigau, Rui Wang-Sattler, Karsten Suhre, Annette Peters, Barbara Thorand, Christian Herder, Wolfgang Rathmann, Michael Roden, Christian Gieger, Mark H H Kramer, Diana van Heemst, Helle K Pedersen, Valborg Gudmundsdottir, Matthias B Schulze, Tobias Pischon, Eco J C de Geus, Heiner Boeing, Dorret I Boomsma, Anette G Ziegler, P Eline Slagboom, Sandra Hummel, Marian Beekman, Harald Grallert, Søren Brunak, Mark I McCarthy, Ramneek Gupta, Ewan R Pearson, Jerzy Adamski, Leen M 't Hart
AIMS/HYPOTHESIS: Circulating metabolites have been shown to reflect metabolic changes during the development of type 2 diabetes. In this study we examined the association of metabolite levels and pairwise metabolite ratios with insulin responses after glucose, glucagon-like peptide-1 (GLP-1) and arginine stimulation. We then investigated if the identified metabolite ratios were associated with measures of OGTT-derived beta cell function and with prevalent and incident type 2 diabetes...
September 21, 2017: Diabetologia
https://www.readbyqxmd.com/read/28933769/a-lanosteryl-triterpene-from-protorhus-longifolia-improves-glucose-tolerance-and-pancreatic-beta-cell-ultrastructure-in-type-2-diabetic-rats
#4
Sihle E Mabhida, Rebamang A Mosa, Dambudzo Penduka, Foluso O Osunsanmi, Phiwayinkosi V Dludla, Tryana G Djarova, Andy R Opoku
Type 2 diabetes remains one of the leading causes of death worldwide. Persistent hyperglycemia within a diabetic state is implicated in the generation of oxidative stress and aggravated inflammation that is responsible for accelerated modification of pancreatic beta cell structure. Here we investigated whether a lanosteryl triterpene, methyl-3β-hydroxylanosta-9,24-dien-21-oate (RA-3), isolated from Protorhus longifolia can improve glucose tolerance and pancreatic beta cell ultrastructure by reducing oxidative stress and inflammation in high fat diet and streptozotocin-induced type 2 diabetes in rats...
July 26, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28932877/when-beta-cells-talk-back
#5
EDITORIAL
Heather C Denroche, Dominika Nackiewicz, C Bruce Verchere
No abstract text is available yet for this article.
September 20, 2017: Diabetologia
https://www.readbyqxmd.com/read/28932254/branched-chain-amino-acid-supplementation-restores-reduced-insulinotropic-activity-of-a-low-protein-diet-through-the-vagus-nerve-in-rats
#6
Mami Horiuchi, Tomoya Takeda, Hiroyuki Takanashi, Yori Ozaki-Masuzawa, Yusuke Taguchi, Yuka Toyoshima, Lila Otani, Hisanori Kato, Meri Sone-Yonezawa, Fumihiko Hakuno, Shin-Ichiro Takahashi, Asako Takenaka
BACKGROUND: Previously, we reported that a low-protein diet significantly reduced insulin secretion in response to feeding within 1 h in rats, suggesting that the insulinotropic effect of dietary protein plays an important role in maintaining normal insulin release. The current study aimed to elucidate whether deficiency of certain amino acids could diminish the insulinotropic activity and to investigate whether reduced insulin secretion in response to a low-protein diet is restored by supplementation with certain amino acids...
2017: Nutrition & Metabolism
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
#7
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/28931519/beta-cell-replacement-in-mice-using-human-type-1-diabetes-nuclear-transfer-embryonic-stem-cells
#8
Lina Sui, Nichole Danzl, Sean R Campbell, Ryan Viola, Damian Williams, Yuan Xing, Yong Wang, Neil Phillips, Greg Poffenberger, Bjarki Johannesson, Jose Oberholzer, Alvin C Powers, Rudolph L Leibel, Xiaojuan Chen, Megan Sykes, Dieter Egli
Beta cells derived from stem cells hold great promise for cell replacement therapy for diabetes. Here we examine the ability of nuclear transfer embryonic stem cells (NT-ES) derived from a type 1 diabetes patient to differentiate into beta cells, and provide a source of autologous islets for cell replacement. NT-ES cells differentiate in vitro with an average efficiency of 55% into C-peptide-positive cells, expressing markers of mature beta cells, including MAFA and NKX6.1. Upon transplantation in immunodeficient mice, grafted cells form vascularized islet-like structures containing MAFA/C-peptide-positive cells...
September 20, 2017: Diabetes
https://www.readbyqxmd.com/read/28929027/the-role-of-polycarbonate-monomer-bisphenol-a-in-insulin-resistance
#9
Milos Pjanic
Bisphenol A (BPA) is a synthetic unit of polycarbonate polymers and epoxy resins, the types of plastics that could be found in essentially every human population and incorporated into almost every aspect of the modern human society. BPA polymers appear in a wide range of products, from liquid storages (plastic bottles, can and glass linings, water pipes and tanks) and food storages (plastics wraps and containers), to medical and dental devices. BPA polymers could be hydrolyzed spontaneously or in a photo- or temperature-catalyzed process, providing widespread environmental distribution and chronic exposure to the BPA monomer in contemporary human populations...
2017: PeerJ
https://www.readbyqxmd.com/read/28925365/generation-of-an-induced-pluripotent-stem-cell-ipsc-line-from-a-patient-with-maturity-onset-diabetes-of-the-young-type-13-mody13-with-a-the-potassium-inwardly-rectifying-channel-subfamily-j-member-11-kcnj11-mutation
#10
Frank Griscelli, Olivier Feraud, Tony Ernault, Noufissa Oudrihri, Ali G Turhan, Amélie Bonnefond, Philippe Froguel, Annelise Bennaceur-Griscelli
Heterozygous activating mutation (p.Glu227Lys) in KCNJ11 leads to maturity-onset diabetes of the young (MODY) type 13, that is a subtype of dominant inherited young-onset non-autoimmune diabetes due to a primary defect in pancreatic beta cells. We generated induced pluripotent stem cells (iPSCs) from a patient with KCNJ11(p.Glu227Lys) mutation who developed MODY at 13years old. KCNJ11(p.Glu227Lys)-mutated cells that were reprogrammed by non-integrative viral transduction had normal karyotype, harboured the KCNJ11(p...
August 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28924486/expression-of-transcription-factors-in-men1-associated-pancreatic-neuroendocrine-tumors
#11
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/28923327/vitamin-e-deficiency-and-oxidative-status-are-associated-with-prediabetes-in-apparently-healthy-subjects
#12
Gabriela Rodríguez-Ramírez, Luis E Simental-Mendía, Manuela de la A Carrera-Gracia, Martha-Angélica Quintanar-Escorza
BACKGROUND: Previous studies have indicated that vitamin E deficiency and oxidative stress affect the beta cell function. Hence, the aim of this study was to determine the association between vitamin E deficiency and oxidative status with prediabetes in apparently healthy subjects. METHODS: Apparently healthy men and women aged 18-65 years were enrolled in a case-control study. Individuals with new diagnosis of prediabetes were considered as cases and compared with a control group of individuals with normal glucose tolerance...
April 2017: Archives of Medical Research
https://www.readbyqxmd.com/read/28921917/changes-on-the-pancreas-in-experimental-diabetes-and-the-effect-of-lycopene-on-these-changes-pdx-1-ngn-3-and-nestin-expressions
#13
Mustafa Sandıkcı, Levent Karagenc, Mustafa Yıldız
The aim of the present study was to investigate changes occurring in the number of beta cells, as well as the expressions of Ngn-3, nestin and Pdx-1 of pancreatic progenitor cells in the pancreas of experimentally-induced adult diabetic rats and to determine the effect of orally-administered lycopene on these changes. Following the administration of 50 mg/kg streptozotocin to rats, four groups of animals were established: control+corn oil, control+lycopene, diabetic+corn oil and diabetic+lycopene. The animals in the control+lycopene and diabetic+lycopene groups received 4 mg/kg lycopene for a period of four weeks...
September 16, 2017: Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology
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
#14
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/28918470/assessment-of-glucose-regulation-in-pregnancy-after-gastric-bypass-surgery
#15
Christian S Göbl, Latife Bozkurt, Andrea Tura, Michael Leutner, Laura Andrei, Lukas Fahr, Peter Husslein, Wolfgang Eppel, Alexandra Kautzky-Willer
AIMS/HYPOTHESIS: Roux-en-Y gastric bypass (RYGB) surgery is characterised by glycaemic variability. Prospective studies of glucose metabolism in pregnancy after RYGB are not available, therefore this study aimed to evaluate physiological alterations in glucose metabolism in pregnancy following RYGB. METHODS: Sixty-three pregnant women (25 who underwent RYGB, 19 non-operated obese control women and 19 normal weight control women) were included. Frequently sampled 3 h OGTTs and 1 h IVGTTs were performed between 24 and 28 weeks of gestation and, in a subgroup, were repeated at 3-6 months after delivery...
September 16, 2017: Diabetologia
https://www.readbyqxmd.com/read/28914811/leptolide-improves-insulin-resistance-in-diet-induced-obese-mice
#16
Pablo Villa-Pérez, Mercedes Cueto, Ana R Díaz-Marrero, Carmen D Lobatón, Alfredo Moreno, Germán Perdomo, Irene Cózar-Castellano
Type 2 diabetes (T2DM) is a complex disease linked to pancreatic beta-cell failure and insulin resistance. Current antidiabetic treatment regimens for T2DM include insulin sensitizers and insulin secretagogues. We have previously demonstrated that leptolide, a member of the furanocembranolides family, promotes pancreatic beta-cell proliferation in mice. Considering the beneficial effects of leptolide in diabetic mice, in this study, we aimed to address the capability of leptolide to improve insulin resistance associated with the pathology of obesity...
September 15, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28911974/molecular-genetics-of-the-transcription-factor-glis3-identifies-its-dual-function-in-beta-cells-and-neurons
#17
Sophie Calderari, Massimiliano Ria, Christelle Gérard, Tatiane C Nogueira, Olatz Villate, Stephan C Collins, Helen Neil, Nicolas Gervasi, Christophe Hue, Nicolas Suarez-Zamorano, Cécilia Prado, Miriam Cnop, Marie-Thérèse Bihoreau, Pamela J Kaisaki, Jean-Baptiste Cazier, Cécile Julier, Mark Lathrop, Michel Werner, Decio L Eizirik, Dominique Gauguier
The GLIS family zinc finger 3 isoform (GLIS3) is a risk gene for Type 1 and Type 2 diabetes, glaucoma and Alzheimer's disease endophenotype. We identified GLIS3 binding sites in insulin secreting cells (INS1) (FDR q<0.05; enrichment range 1.40-9.11 fold) sharing the motif wrGTTCCCArTAGs, which were enriched in genes involved in neuronal function and autophagy and in risk genes for metabolic and neuro-behavioural diseases. We confirmed experimentally Glis3-mediated regulation of the expression of genes involved in autophagy and neuron function in INS1 and neuronal PC12 cells...
September 11, 2017: Genomics
https://www.readbyqxmd.com/read/28911206/identification-of-the-molecular-dysfunction-caused-by-glutamate-dehydrogenase-s445l-mutation-responsible-for-hyperinsulinism-hyperammonemia
#18
Mariagrazia Grimaldi, Melis Karaca, Livia Latini, Estelle Brioudes, Thomas Schalch, Pierre Maechler
Congenital hyperinsulinism/hyperammonemia (HI/HA) syndrome gives rise to unregulated protein-induced insulin secretion from pancreatic beta-cells, fasting hypoglycemia and elevated plasma ammonia levels. Mutations associated with HI/HA were identified in the Glud1 gene, encoding for glutamate dehydrogenase (GDH). We aimed at identifying the molecular causes of dysregulation in insulin secretion and ammonia production conferred by the most frequent HI/HA mutation Ser445Leu. Following transduction with adenoviruses carrying the human GDH-wild type or GDH-S445L-mutant gene, immunoblotting showed efficient expression of the transgenes in all the investigated cell types...
September 15, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28900540/treatment-of-diabetic-mice-with-the-sglt2-inhibitor-ta-1887-antagonizes-diabetic-cachexia-and-decreases-mortality
#19
Taichi Sugizaki, Shunshun Zhu, Ge Guo, Akiko Matsumoto, Jiabin Zhao, Motoyoshi Endo, Haruki Horiguchi, Jun Morinaga, Zhe Tian, Tsuyoshi Kadomatsu, Keishi Miyata, Hiroshi Itoh, Yuichi Oike
A favorable effect of an inhibitor of the sodium-glucose cotransporter 2 (SGLT2i) on mortality of diabetic patients was recently reported, although mechanisms underlying that effect remained unclear. Here, we examine SGLT2i effects on survival of diabetic mice and assess factors underlying these outcomes. To examine SGLT2i treatment effects in a model of severe diabetes, we fed genetically diabetic db/db mice a high-fat diet and then assessed outcomes including diabetic complications between SGLT2i TA-1887-treated and control mice...
2017: NPJ Aging and Mechanisms of Disease
https://www.readbyqxmd.com/read/28898241/alterations-in-the-programming-of-energy-metabolism-in-adolescents-with-background-exposure-to-dioxins-dl-pcbs-and-pbdes
#20
Marike M Leijs, Janna G Koppe, Thomas Vulsma, Kees Olie, Wim M C van Aalderen, Pim de Voogt, Juliette Legler, Gavin W Ten Tusscher
OBJECTIVES: Dioxins and PCBs are highly toxic and persistent environmental pollutants that are measurable in humans worldwide. These persistent organic pollutants are associated with a higher incidence of diabetes mellitus. We hypothesise that perinatal (background) exposure to industrial pollutants like dioxins also influences body mass development and energy metabolism in later life. STUDY DESIGN: In The Netherlands, the perinatal exposure (prenatal exposure and postnatal lactational intake) to dioxins has been studied prospectively since 1987...
2017: PloS One
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