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https://www.readbyqxmd.com/read/29341865/evidence-of-genetic-predisposition-for-metabolically-healthy-obesity-and-metabolically-obese-normal-weight
#1
Lam Opal Huang, Ruth Loos, Tuomas Oskari Kilpeläinen
Obesity has evolved into a global pandemic, which constitutes a major threat to public health. The majority of obesity-related health care costs are due to cardiometabolic complications, such as insulin resistance, dyslipidemia, and hypertension, which are risk factors for type 2 diabetes and cardiovascular disease. However, many obese individuals, often called metabolically healthy obese (MHO), seem to be protected from these cardiometabolic complications. Conversely, there is a group of individuals who suffer from cardiometabolic complications despite being of normal weight; a condition termed metabolically obese normal weight (MONW)...
December 20, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/29341416/resveratrol-influences-pancreatic-islets-by-opposing-effects-on-electrical-activity-and-insulin-release
#2
Simone Brouwer, Theresa Hoffmeister, Anne Gresch, Lisa Schönhoff, Martina Düfer
SCOPE: Resveratrol is suggested to improve glycemic control by activation of sirtuin 1 (SIRT1) and has already been tested clinically. Our investigation characterizes the targets of resveratrol in pancreatic beta cells and their contribution to short- and long-term effects on insulin secretion. METHODS AND RESULTS: Islets or beta cells were isolated from C57Bl/6N mice. Electrophysiology was performed with microelectrode arrays and patch-clamp technique, insulin secretion and content were determined by radioimmunoassay, cAMP was measured by enzyme-linked immunosorbent assay and cytosolic Ca2+ concentration by fluorescence methods...
January 17, 2018: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/29330559/a-post-translational-balancing-act-the-good-and-the-bad-of-sumoylation-in-pancreatic-islets
#3
EDITORIAL
Patrick E MacDonald
Post-translational modification of proteins contributes to the control of cell function and survival. The balance of these in insulin-producing pancreatic beta cells is important for the maintenance of glucose homeostasis. Protection from the damaging effects of reactive oxygen species is required for beta cell survival, but if this happens at the expense of insulin secretory function then the ability of islets to respond to changing metabolic conditions may be compromised. In this issue of Diabetologia, He et al ( https://doi...
January 12, 2018: Diabetologia
https://www.readbyqxmd.com/read/29329447/congenital-hyperinsulinism-and-hypopituitarism-attributable-to-a-novel-mutation-in-foxa2
#4
Mary Ellen Vajravelu, Jinghua Chai, Bryan Krock, Samuel Baker, David Langdon, Craig Alter, Diva D De León
Context: Persistent hypoglycemia in the newborn period most commonly occurs due to hyperinsulinism. The phenotype of hypoketotic hypoglycemia can also result from pituitary hormone deficiencies, including growth hormone and adrenocorticotropic hormone deficiency. Forkhead box A2 (Foxa2) is a transcription factor shown in mouse models to influence insulin secretion by pancreatic beta cells. In addition, Foxa2 is involved in regulation of pituitary development, and deletions of FOXA2 have been linked to panhypopituitarism...
January 10, 2018: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29327400/a-vitamin-b12-conjugate-of-exendin-4-improves-glucose-tolerance-without-associated-nausea-or-hypophagia-in-rodents
#5
Elizabeth G Mietlicki-Baase, Claudia G Liberini, Jayme L Workinger, Ron L Bonaccorso, Tito Borner, David J Reiner, Kieran Koch-Laskowski, Lauren E McGrath, Rinzin Lhamo, Lauren M Stein, Bart C De Jonghe, George G Holz, Christian L Roth, Robert P Doyle, Matthew R Hayes
AIMS: While pharmacological glucagon-like peptide-1 receptor (GLP-1R) agonists are FDA-approved for treating type 2 diabetes mellitus (T2DM) and obesity, a major side effect is nausea/malaise. We recently developed a conjugate of vitamin B12 bound to the GLP-1R agonist exendin-4 (Ex4), which displays enhanced proteolytic stability and retention of GLP-1R agonism. Here, we evaluate whether the conjugate (B12-Ex4) can improve glucose tolerance without producing anorexia and malaise. MATERIALS AND METHODS: We evaluated the effects of systemic B12-Ex4 and unconjugated Ex4 on food intake and body weight change, oral glucose tolerance, and nausea/malaise in male rats, and on intraperitoneal glucose tolerance in mice...
January 12, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29325720/development-of-pancreatic-machine-perfusion-translational-steps-from-porcine-to-human-models
#6
Karim Hamaoui, Sally Gowers, Bynvant Sandhu, Natalie Vallant, Terry Cook, Martyn Boutelle, Daniel Casanova, Vassilios Papalois
BACKGROUND: Hypothermic machine perfusion (HMP) is increasingly being used for extended criteria kidney grafts. Pancreatic HMP is challenging because physiologically the pancreas is a low-flow organ susceptible to edema. We report the successful development of preclinical HMP models using porcine pancreases, as well as human pancreases unsuitable for clinical transplantation. METHODS: Ten porcine pancreases were used in the development of these perfusion models...
January 8, 2018: Journal of Surgical Research
https://www.readbyqxmd.com/read/29322219/sirt6-mediated-transcriptional-suppression-of-txnip-is-critical-for-pancreatic-beta-cell-function-and-survival-in-mice
#7
Kunhua Qin, Ning Zhang, Zhao Zhang, Michael Nipper, Zhenxin Zhu, Jake Leighton, Kexin Xu, Nicolas Musi, Pei Wang
AIMS/HYPOTHESIS: Better understanding of how genetic and epigenetic components control beta cell differentiation and function is key to the discovery of novel therapeutic approaches to prevent beta cell dysfunction and failure in the progression of type 2 diabetes. Our goal was to elucidate the role of histone deacetylase sirtuin 6 (SIRT6) in beta cell development and homeostasis. METHODS: Sirt6 endocrine progenitor cell conditional knockout and beta cell-specific knockout mice were generated using the Cre-loxP system...
January 10, 2018: Diabetologia
https://www.readbyqxmd.com/read/29306997/extracellular-matrix-molecules-and-their-potential-contribution-to-the-function-of-transplanted-pancreatic-islets
#8
REVIEW
L Alberto Llacua, Marijke M Faas, Paul de Vos
Extracellular matrix (ECM) molecules are responsible for structural and biochemical support, as well as for regulation of molecular signalling and tissue repair in many organ structures, including the pancreas. In pancreatic islets, collagen type IV and VI, and laminins are the most abundant molecules, but other ECM molecules are also present. The ECM interacts with specific combinations of integrin α/β heterodimers on islet cells and guides many cellular processes. More specifically, some ECM molecules are involved in beta cell survival, function and insulin production, while others can fine tune the susceptibility of islet cells to cytokines...
January 6, 2018: Diabetologia
https://www.readbyqxmd.com/read/29305625/ifn-%C3%AE-induces-a-preferential-long-lasting-expression-of-mhc-class-i-in-human-pancreatic-beta-cells
#9
Alexandra Coomans de Brachène, Reinaldo S Dos Santos, Laura Marroqui, Maikel L Colli, Lorella Marselli, Raghavendra G Mirmira, Piero Marchetti, Decio L Eizirik
AIMS/HYPOTHESIS: IFN-α, a cytokine expressed in human islets from individuals affected by type 1 diabetes, plays a key role in the pathogenesis of diabetes by upregulating inflammation, endoplasmic reticulum (ER) stress and MHC class I overexpression, three hallmarks of islet histology in early type 1 diabetes. We tested whether expression of these mediators of beta cell loss is reversible upon IFN-α withdrawal or IFN-α pathway inhibition. METHODS: IFN-α-induced MHC class I overexpression, ER stress and inflammation were evaluated by flow cytometry, immunofluorescence and real-time PCR in human EndoC-βH1 cells or human islets exposed to IFN-α with or without the presence of Janus kinase (JAK) inhibitors...
January 5, 2018: Diabetologia
https://www.readbyqxmd.com/read/29304344/endogenous-reprogramming-of-alpha-cells-into-beta-cells-induced-by-viral-gene-therapy-reverses-autoimmune-diabetes
#10
Xiangwei Xiao, Ping Guo, Chiyo Shiota, Ting Zhang, Gina M Coudriet, Shane Fischbach, Krishna Prasadan, Joseph Fusco, Sabarinathan Ramachandran, Piotr Witkowski, Jon D Piganelli, George K Gittes
Successful strategies for treating type 1 diabetes need to restore the function of pancreatic beta cells that are destroyed by the immune system and overcome further destruction of insulin-producing cells. Here, we infused adeno-associated virus carrying Pdx1 and MafA expression cassettes through the pancreatic duct to reprogram alpha cells into functional beta cells and normalized blood glucose in both beta cell-toxin-induced diabetic mice and in autoimmune non-obese diabetic (NOD) mice. The euglycemia in toxin-induced diabetic mice and new insulin+ cells persisted in the autoimmune NOD mice for 4 months prior to reestablishment of autoimmune diabetes...
January 4, 2018: Cell Stem Cell
https://www.readbyqxmd.com/read/29304337/alpha-to-beta-cell-reprogramming-stepping-toward-a-new-treatment-for-diabetes
#11
Anna B Osipovich, Mark A Magnuson
Beta cell replacement strategies hold promise for permanently treating type 1 diabetes. In Cell Stem Cell, Xiao et al. (2018) restore pancreatic beta cell mass and normalize blood glucose in diabetic mice by reprogramming pancreatic alpha to beta cells using Pdx1- and Mafa-expressing adeno-associated virus infused into the pancreatic duct.
January 4, 2018: Cell Stem Cell
https://www.readbyqxmd.com/read/29299635/both-conditional-ablation-and-overexpression-of-e2-sumo-conjugating-enzyme-ubc9-in-mouse-pancreatic-beta-cells-result-in-impaired-beta-cell-function
#12
Xiaoyu He, Qiaohong Lai, Cai Chen, Na Li, Fei Sun, Wenting Huang, Shu Zhang, Qilin Yu, Ping Yang, Fei Xiong, Zhishui Chen, Quan Gong, Boxu Ren, Jianping Weng, Décio L Eizirik, Zhiguang Zhou, Cong-Yi Wang
AIMS/HYPOTHESIS: Post-translational attachment of a small ubiquitin-like modifier (SUMO) to the lysine (K) residue(s) of target proteins (SUMOylation) is an evolutionary conserved regulatory mechanism. This modification has previously been demonstrated to be implicated in the control of a remarkably versatile regulatory mechanism of cellular processes. However, the exact regulatory role and biological actions of the E2 SUMO-conjugating enzyme (UBC9)-mediated SUMOylation function in pancreatic beta cells has remained elusive...
January 3, 2018: Diabetologia
https://www.readbyqxmd.com/read/29298842/pick1-is-essential-for-insulin-production-and-the-maintenance-of-glucose-homeostasis
#13
Jia Li, Zhuo Mao, Jiandong Huang, Jun Xia
Protein interacting with C-kinase 1 (PICK1) is a peripheral membrane protein that controls insulin granule formation, trafficking and maturation in INS-1E cells. However, global Pick1-knockout mice only showed a subtle, diabetes-like phenotype. This raises the possibility that compensatory effects from tissues other than pancreatic beta cells may obscure the effects of insulin deficiency. To explore the role of PICK1 in pancreatic islets, we generated mice harboring a conditional Pick1 allele in a C57BL/6J background...
January 3, 2018: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29290993/microrna-34c-acts-as-a-bidirectional-switch-in-the-maturation-of-insulin-producing-cells-derived-from-mesenchymal-stem-cells
#14
Chunyu Bai, Yuhua Gao, Xiangyang Zhang, Wancai Yang, Weijun Guan
miRNAs regulate insulin secretion, pancreatic development, and beta-cell differentiation. However, their function in the differentiation of IPCs from MSCs is poorly understood. In this study, to screen for miRNAs and their targets that function during the formation of IPCs from MSCs, we examined the miRNA expression profiles of MSCs and IPCs using RNA-seq and qPCR to confirm the above results. We found that miR-34c exhibited transient upregulation at an early stage of the formation of IPCs derived from MSCs...
December 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/29289465/investigating-the-role-of-transcription-factors-of-pancreas-development-in-pancreatic-cancer
#15
REVIEW
Ahmad Abu Turab Naqvi, Gulam Mustafa Hasan, Md Imtaiyaz Hassan
Pancreatic cancer (PC) is the seventh most common cause of cancer-related deaths worldwide that kills more than 300,000 people every year. Prognosis of PC is very poor with a five-year survival rate about 5%. The most common and highly observed type of PC is pancreatic ductal adenocarcinoma (PDAC). It is preceded by the progression of precursor lesions such as Pancreatic Intraepithelial Neoplasia (PanIN), Intraductal Papillary Neoplasm (IPMN) and Mucinous Cystic Neoplasm (MCN). PanIN is the most common among these premalignant lesions...
December 24, 2017: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
https://www.readbyqxmd.com/read/29289049/coexistence-between-silent-and-bursting-states-in-a-biophysical-hodgkin-huxley-type-of-model
#16
Nataliya Stankevich, Erik Mosekilde
Classification of the dynamical mechanisms that support bistability between bursting oscillations and silence has not yet been clarified in detail. The purpose of this paper is to demonstrate that the coexistence of a stable equilibrium point with a state of continuous bursting can occur in a slightly modified, biophysical model that describe the dynamics of pancreatic beta-cells. To realize this form of coexistence, we have introduced an additional voltage-dependent potassium current that is activated in the region around the original, unstable equilibrium point...
December 2017: Chaos
https://www.readbyqxmd.com/read/29288549/transplantation-of-macro-encapsulated-human-islets-within-the-bioartificial-pancreas-%C3%AE-air-to-patients-with-type-1-diabetes-mellitus
#17
Per-Ola Carlsson, Daniel Espes, Amir Sedigh, Avi Rotem, Baruch Zimermann, Helena Grinberg, Tali Goldman, Uriel Barkai, Yuval Avni, Gunilla T Westermark, Lina Carlbom, Håkan Ahlström, Olof Eriksson, Johan Olerud, Olle Korsgren
Macroencapsulation devices provide the dual possibility to immunoprotect transplanted cells while also being retrievable; the latter bearing importance for safety in future trials with stem-cell derived cells. However, macroencapsulation entails a problem with oxygen supply to the encapsulated cells. The βAir device solves this with an incorporated refillable oxygen tank. This phase 1 study evaluated the safety and efficacy of implanting the βAir device containing allogeneic human pancreatic islets to patients with type 1 diabetes...
December 29, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/29285014/microrna-503-contribute-to-pancreatic-beta-cell-dysfunction-by-targeting-the-mtor-pathway-in-gestational-diabetes-mellitus
#18
Ke Xu, Dezhi Bian, Lanxiang Hao, Fei Huang, Min Xu, Jie Qin, Yanmei Liu
Loss of pancreatic β cells is involved in pathogenesis of gestational diabetes mellitus (GDM). Recently, several studies have elucidated the connection between microRNAs (miRNAs) and diabetes mellitus (DM), but the role of miRNAs in GDM remains unclear. The aim of this study was to evaluate the potential functions of miRNAs in GDM and to investigate the underlying mechanisms of action. First, we explored the expression profile of miRNAs in placenta tissue from GDM patients using microarray. Validation analysis was performed in peripheral blood specimens using quantitative reverse transcription PCR (qRT-PCR)...
2017: EXCLI Journal
https://www.readbyqxmd.com/read/29285009/the-relation-between-rice-consumption-arsenic-contamination-and-prevalence-of-diabetes-in-south-asia
#19
REVIEW
Fatima Ismail Hassan, Kamal Niaz, Fazlullah Khan, Faheem Maqbool, Mohammad Abdollahi
Rice is the major staple food for about two billion people living in Asia. It has been reported to contain considerable amount of inorganic arsenic which is toxic to pancreatic beta cells and disrupt glucose homeostasis. Articles and conference papers published between 1992 and 2017, indexed in Scopus, PubMed, EMBASE, Google, and Google scholar were used. Arsenic exposure has been associated with increased blood glucose and insulin levels, or decreased sensitization of insulin cells to glucose uptake. Several studies have shown the association between inorganic arsenic exposure and incidence of diabetes mellitus...
2017: EXCLI Journal
https://www.readbyqxmd.com/read/29284659/a-targeted-rnai-screen-identifies-endocytic-trafficking-factors-that-control-glp-1-receptor-signaling-in-pancreatic-beta-cells
#20
Teresa Buenaventura, Nisha Kanda, Phoebe C Douzenis, Ben Jones, Stephen R Bloom, Pauline Chabosseau, Ivan R Corrêa, Domenico Bosco, Lorenzo Piemonti, Piero Marchetti, Paul R Johnson, Am James Shapiro, Guy A Rutter, Alejandra Tomas
The GLP-1 receptor (GLP-1R) is a key target for type 2 diabetes (T2D) treatment. Since endocytic trafficking of agonist-bound receptors is one of the most important routes for regulation of receptor signaling, a better understanding of this process may facilitate the development of new T2D therapeutic strategies. Here, we have screened 29 proteins with known functions in G protein-coupled receptor trafficking for their role in GLP-1R potentiation of insulin secretion in pancreatic beta cells. We identify five (clathrin, dynamin1, AP2, SNX27 and SNX1) that increase and four (HIP1, HIP14, GASP-1 and Nedd4) that decrease insulin secretion from murine insulinoma MIN6B1 cells in response to the GLP-1 analogue exendin-4...
December 28, 2017: Diabetes
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