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https://www.readbyqxmd.com/read/28812213/heterogeneity-in-the-beta-cell-population-a-guided-search-into-its-significance-in-pancreas-and-in-implants
#1
REVIEW
Daniel Pipeleers, Ines De Mesmaeker, Thomas Robert, Freya Van Hulle
PURPOSE OF REVIEW: Intercellular differences in function have since long been noticed in the pancreatic beta-cell population. Heterogeneity in cellular glucose responsiveness is considered of physiological and pathological relevance. The present review updates evidence for the physiologic significance of beta-cell heterogeneity in the pancreas. It also briefly discusses what this role would imply for beta-cell implants in diabetes. RECENT FINDINGS: Over the past 3 years, functionally different beta cells have been related to mechanisms that may underlie their heterogeneity in the pancreas, such as the stage in their life cycle and the degree of their clustering to islets with varying vascularization...
August 15, 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/28796938/effect-of-intrapancreatic-fat-on-diabetes-outcomes-after-total-pancreatectomy-with-islet-autotransplantation
#2
Muhammed Kizilgul, Joshua J Wilhelm, Gregory J Beilman, Srinath Chinnakotla, Ty B Dunn, Timothy L Pruett, Muhamad Abdulla, David Heller, Martin L Freeman, Sarah J Schwarzenberg, Bernhard J Hering, Melena D Bellin
BACKGROUND: Pancreatic fat might adversely affect beta-cell mass and function, possibly via the local release of non-esterified fatty acids (NE-FAs) and pro-inflammatory and vasoactive factors released by adipose tissue, however, the impact of intrapancreatic fat has never been studied in patients with pancreatitis undergoing total pancreatectomy with islet autotransplantation (TPIAT). We aimed to test whether pancreatic fatty infiltration has a negative effect on metabolic outcomes following TPIAT METHODS: We studied the association between pancreatic fatty infiltration and diabetes outcomes in 79 patients undergoing TPIAT with low (LPF; n = 53) or high (HPF; n = 26) pancreatic fat content...
August 10, 2017: Journal of Diabetes
https://www.readbyqxmd.com/read/28793277/o-2-18-f-fluoroethyl-l-tyrosine-18-f-fet-uptake-in-insulinoma-first-results-from-a-xenograft-mouse-model-and-from-human
#3
Alessio Imperiale, Frédéric Boisson, Guillaume Kreutter, Bernard Goichot, Izzie Jacques Namer, Philippe Bachellier, Patrice Laquerriere, Laurence Kessler, Patrice Marchand, David Brasse
INTRODUCTION: Herein we have evaluated the uptake of O-(2-(18)F-fluoroethyl)-l-tyrosine ((18)F-FET) in insulinoma in comparison with those of 6-(18)F-fluoro-3,4-dihydroxy-l-phenylalanine ((18)F-FDOPA) providing first data from both murine xenograft model and one patient with proved endogenous hyperinsulinemic hypoglycemia. METHODS: Dynamic (18)F-FET and carbidopa-assisted (18)F-FDOPA PET were performed on tumor-bearing nude mice after subcutaneous injection of RIN-m5F murine beta cells and on a 30-year-old man with type-1 multiple endocrine neoplasia and hyperinsulinemic hypoglycemia defined by a positive fasting test...
July 12, 2017: Nuclear Medicine and Biology
https://www.readbyqxmd.com/read/28792951/how-stable-is-repression-of-disallowed-genes-in-pancreatic-islets-in-response-to-metabolic-stress
#4
Katleen Lemaire, Mikaela Granvik, Anica Schraenen, Lotte Goyvaerts, Leentje Van Lommel, Ana Gómez-Ruiz, Peter In 't Veld, Patrick Gilon, Frans Schuit
The specific phenotype of mature differentiated beta cells not only depends on the specific presence of genes that allow beta cell function but also on the selective absence of housekeeping genes ("disallowed genes") that would interfere with this function. Recent studies have shown that both histone modifications and DNA methylation via the de novo methyltransferase DNMT3A are involved in repression of disallowed genes in neonatal beta cells when these cells acquire their mature phenotype. It is unknown, however, if the environmental influence of advanced age, pregnancy and the metabolic stress of high fat diet or diabetes could alter the repression of disallowed genes in beta cells...
2017: PloS One
https://www.readbyqxmd.com/read/28791439/metabolic-crosstalk-between-fatty-pancreas-and-fatty-liver-effects-on-local-inflammation-and-insulin-secretion
#5
Felicia Gerst, Robert Wagner, Gabriele Kaiser, Madhura Panse, Martin Heni, Jürgen Machann, Malte N Bongers, Tina Sartorius, Bence Sipos, Falko Fend, Christian Thiel, Silvio Nadalin, Alfred Königsrainer, Norbert Stefan, Andreas Fritsche, Hans-Ulrich Häring, Susanne Ullrich, Dorothea Siegel-Axel
AIMS/HYPOTHESIS: Obesity-linked ectopic fat accumulation is associated with the development of type 2 diabetes. Whether pancreatic and liver steatosis impairs insulin secretion is controversial. We examined the crosstalk of human pancreatic fat cells with islets and the role of diabetogenic factors, i.e. palmitate and fetuin-A, a hepatokine released from fatty liver. METHODS: Human pancreatic resections were immunohistochemically stained for insulin, glucagon, somatostatin and the macrophage/monocyte marker CD68...
August 8, 2017: Diabetologia
https://www.readbyqxmd.com/read/28790184/adiponectin-protects-against-development-of-metabolic-disturbances-in-a-pcos-mouse-model
#6
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 8, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28790139/islet-amyloid-deposits-preferentially-in-the-highly-functional-and-most-blood-perfused-islets
#7
Sara Ullsten, Sara Bohman, Marie E Oskarsson, K Peter R Nilsson, Gunilla Westermark, Per-Ola Carlsson
Islet amyloid and beta cell death in type 2 diabetes are heterogeneous events, where some islets are affected early in the disease process whereas others remain visibly unaffected. This study investigated the possibility that inter-islet functional and vascular differences may explain the propensity for amyloid accumulation in certain islets. Highly blood perfused islets were identified by microspheres in human islet amyloid polypeptide expressing mice fed a high-fat diet for three or 10 months. These highly blood perfused islets had better glucose-stimulated insulin secretion capacity than other islets, and developed more amyloid deposits after 10 months of high-fat diet...
August 8, 2017: Endocrine Connections
https://www.readbyqxmd.com/read/28775287/non-invasive-in-vivo-determination-of-viable-islet-graft-volume-by-111-in-exendin-3
#8
Wael A Eter, Inge Van der Kroon, Karolina Andralojc, Mijke Buitinga, Stefanie M A Willekens, Cathelijne Frielink, Desiree Bos, Lieke Joosten, Otto C Boerman, Maarten Brom, Martin Gotthardt
Pancreatic islet transplantation is a promising therapy for patients with type 1 diabetes. However, the duration of long-term graft survival is limited due to inflammatory as well as non-inflammatory processes and routine clinical tests are not suitable to monitor islet survival. (111)In-exendin-SPECT (single photon emission computed tomography) is a promising method to non-invasively image islets after transplantation and has the potential to help improve the clinical outcome. Whether (111)In-exendin-SPECT allows detecting small differences in beta-cell mass (BCM) and measuring the actual volume of islets that were successfully engrafted has yet to be demonstrated...
August 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28770422/depletion-of-beta-cell-intranuclear-rodlets-in-human-type-ii-diabetes
#9
Yi Yuan Zhou, Soufiane El Hallani, Fady Balaa, Waleed Mohammad, Douglas A Gray, John Woulfe
Intranuclear rodlets (INRs) are rod-shaped intranuclear bodies of unknown function present in the nuclei of pancreatic beta cells. Previous studies have demonstrated a significant depletion of INRs from beta cells in mouse models of type II diabetes, suggesting that they may have pathological significance. The objective of the present study was to determine whether beta cell INRs show quantitative alterations in human type II diabetes. In sections of non-neoplastic pancreas from 23 diabetic patients and 23 controls who had undergone complete or partial pancreatectomy, we detected a significant reduction in the proportion of INRs in insulin-immunoreactive beta cells...
August 2, 2017: Endocrine Pathology
https://www.readbyqxmd.com/read/28770323/understanding-and-preventing-type-1-diabetes-through-the-unique-working-model-of-trialnet
#10
REVIEW
Manuela Battaglia, Mark S Anderson, Jane H Buckner, Susan M Geyer, Peter A Gottlieb, Thomas W H Kay, Åke Lernmark, Sarah Muller, Alberto Pugliese, Bart O Roep, Carla J Greenbaum, Mark Peakman
Type 1 diabetes is an autoimmune disease arising from the destruction of pancreatic insulin-producing beta cells. The disease represents a continuum, progressing sequentially at variable rates through identifiable stages prior to the onset of symptoms, through diagnosis and into the critical periods that follow, culminating in a variable depth of beta cell depletion. The ability to identify the very earliest of these presymptomatic stages has provided a setting in which prevention strategies can be trialled, as well as furnishing an unprecedented opportunity to study disease evolution, including intrinsic and extrinsic initiators and drivers...
August 2, 2017: Diabetologia
https://www.readbyqxmd.com/read/28770320/fgf21-improves-glucose-homeostasis-in-an-obese-diabetes-prone-mouse-model-independent-of-body-fat-changes
#11
Thomas Laeger, Christian Baumeier, Ilka Wilhelmi, Josefine Würfel, Anne Kamitz, Annette Schürmann
AIMS/HYPOTHESIS: Fibroblast growth factor 21 (FGF21) is considered to be a promising therapeutic candidate for the treatment of type 2 diabetes. However, as FGF21 levels are elevated in obese and diabetic conditions we aimed to test if exogenous FGF21 is sufficient to prevent diabetes and beta cell loss in New Zealand obese (NZO) mice, a model for polygenetic obesity and type 2 diabetes. METHODS: Male NZO mice were treated with a specific dietary regimen that leads to the onset of diabetes within 1 week...
August 2, 2017: Diabetologia
https://www.readbyqxmd.com/read/28770318/regulatory-t-cell-dysfunction-in-type-1-diabetes-what-s-broken-and-how-can-we-fix-it
#12
REVIEW
Caroline M Hull, Mark Peakman, Timothy I M Tree
Type 1 diabetes is an autoimmune disease characterised by the destruction of insulin producing beta cells in the pancreas. Whilst it remains unclear what the original triggering factors for this destruction are, observations from the natural history of human type 1 diabetes, including incidence rates in twins, suggest that the disease results from a combination of genetic and environmental factors. Whilst many different immune cells have been implicated, including members of the innate and adaptive immune systems, a view has emerged over the past 10 years that beta cell damage is mediated by the combined actions of CD4(+) and CD8(+) T cells with specificity for islet autoantigens...
August 2, 2017: Diabetologia
https://www.readbyqxmd.com/read/28767692/insulin-receptor-signaling-and-glucagon-like-peptide-1-effects-on-pancreatic-beta-cells
#13
Nunzia Caporarello, Cristina Parrino, Vincenzo Trischitta, Lucia Frittitta
Glucagon-like peptide-1 (GLP-1) is a potent gluco-incretin hormone, which plays a central role on pancreatic beta cell proliferation, survival and insulin secreting activity and whose analogs are used for treating hyperglycemia in type 2 diabetes mellitus. Notably, abnormal insulin signaling affects all the above-mentioned aspects on pancreatic beta cells. The aim of our study was to investigate whether the protective effects of GLP1-1 on beta cells are affected by altered insulin receptor signaling. To this end, several effects of GLP-1 were studied in INS-1E rat beta cells transfected either with an inhibitor of insulin receptor function (i...
2017: PloS One
https://www.readbyqxmd.com/read/28767672/bi-stability-in-type-2-diabetes-mellitus-multi-organ-signalling-network
#14
Shubhankar Kulkarni, Sakshi Sharda, Milind Watve
Type 2 diabetes mellitus (T2DM) is believed to be irreversible although no component of the pathophysiology is irreversible. We show here with a network model that the apparent irreversibility is contributed by the structure of the network of inter-organ signalling. A network model comprising all known inter-organ signals in T2DM showed bi-stability with one insulin sensitive and one insulin resistant attractor. The bi-stability was made robust by multiple positive feedback loops suggesting an evolved allostatic system rather than a homeostatic system...
2017: PloS One
https://www.readbyqxmd.com/read/28765259/glucose-but-not-kcl-diminishes-submembrane-granule-turnover-in-mouse-beta-cells
#15
Dennis Brüning, Kirstin Reckers, Peter Drain, Ingo Rustenbeck
KCl depolarization is widely used to mimic the depolarization during glucose-stimulated insulin secretion. Consequently, the insulin secretion elicited by KCl is often regarded as the equivalent of the first phase of glucose-induced insulin secretion. Here, the effects of both stimuli were compared by measuring the secretion of perifused mouse islets, the cytosolic Ca2+ concentration of single beta-cells and the mobility of submembrane insulin granules by TIRF microscopy of primary mouse beta-cells. Two cargo-directed granule labels were used namely insulin-EGFP and C-peptide-emGFP...
August 1, 2017: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/28764844/biliopancreatic-diversion-with-duodenal-switch-leads-to-better-postprandial-glucose-level-and-beta-cell-function-than-sleeve-gastrectomy-in-individuals-with-type-2-diabetes-very-early-after-surgery
#16
Andréanne Michaud, Thomas Grenier-Larouche, Dominique Caron-Dorval, Simon Marceau, Laurent Biertho, Serge Simard, Denis Richard, André Tchernof, André C Carpentier
OBJECTIVE: The aim of this study was to compare the short-term effect of sleeve gastrectomy (SG) and biliopancreatic diversion with duodenal switch (DS) in order to determine if exclusion of the upper gastrointestinal tract confers greater metabolic improvement, independent of weight loss. METHODS: Standard meals were administered before and on day 3 and 4 after SG to assess insulin sensitivity, β-cell function and gastrointestinal hormone responses in matched normoglycemic (NG) and type 2 diabetes (T2D) participants...
September 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/28763258/cyclin-d2-is-sufficient-to-drive-beta-cell-self-renewal-and-regeneration
#17
Shuen-Ing Tschen, Chun Zeng, Loren Field, Sangeeta Dhawan, Anil Bhushan, Senta Georgia
Diabetes results from an inadequate mass of functional beta cells, due to either beta cell loss caused by autoimmune destruction (Type I diabetes) or beta cell failure in response to insulin resistance (Type II diabetes). Elucidating the mechanisms that regulate beta cell mass may be key to developing new techniques that foster beta cell regeneration as a cellular therapy to treat diabetes. While previous studies concluded that cyclin D2 is required for postnatal beta cell self-renewal in mice, it is not clear if cyclin D2 is sufficient to drive beta cell self-renewal...
August 1, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28763191/nanoporous-immunoprotective-device-for-stem-cell-derived-%C3%AE-cell-replacement-therapy
#18
Ryan Chang, Gaetano Faleo, Holger A Russ, Audrey V Parent, Susanna K Elledge, Daniel A Bernards, Jessica L Allen, Karina Villanueva, Matthias Hebrok, Qizhi Tang, Tejal A Desai
Encapsulation of human embryonic stem-cell-differentiated beta cell clusters (hES-βC) holds great promise for cell replacement therapy for the treatment of diabetics without the need for chronic systemic immune suppression. Here, we demonstrate a nanoporous immunoprotective polymer thin film cell encapsulation device that can exclude immune molecules while allowing exchange of oxygen and nutrients necessary for in vitro and in vivo stem cell viability and function. Biocompatibility studies show the device promotes neovascular formation with limited foreign body response in vivo...
August 7, 2017: ACS Nano
https://www.readbyqxmd.com/read/28762248/engineering-brown-fat-into-skeletal-muscle-using-ultrasound-targeted-microbubble-destruction-gene-delivery-in-obese-zucker-rats-proof-of-concept-design
#19
Raul A Bastarrachea, Jiaxi Chen, Jack W Kent, Edna J Nava-Gonzalez, Ernesto Rodriguez-Ayala, Marcel M Daadi, Barbara Jorge, Hugo Laviada-Molina, Anthony G Comuzzie, Shuyuan Chen, Paul A Grayburn
Ultrasound-targeted microbubble destruction (UTMD) is a novel means of tissue-specific gene delivery. This approach systemically infuses transgenes precoupled to gas-filled lipid microbubbles that are burst within the microvasculature of target tissues via an ultrasound signal resulting in release of DNA and transfection of neighboring cells within the tissue. Previous work has shown that adenovirus containing cDNA of UCP-1, injected into the epididymal fat pads in mice, induced localized fat depletion, improving glucose tolerance, and decreasing food intake in obese diabetic mice...
July 31, 2017: IUBMB Life
https://www.readbyqxmd.com/read/28761107/regulatory-t-cells-from-pancreatic-lymphnodes-of-patients-with-type-1-diabetes-express-increased-levels-of-microrna-mir-125a-5p-that-limits-ccr2-expression
#20
Guido Sebastiani, Giuliana Ventriglia, Angela Stabilini, Carlo Socci, Cristina Morsiani, Andrea Laurenzi, Laura Nigi, Caterina Formichi, Bechara Mfarrej, Alessandra Petrelli, Georgia Fousteri, Todd M Brusko, Francesco Dotta, Manuela Battaglia
Autoimmune type 1 diabetes (T1D) is thought to be caused by a defective immune regulation with regulatory T (Treg) cells playing a fundamental role in this process. Tolerance mechanisms depend on tunable responses that are sensitive to minor perturbations in the expression of molecules that can be carried out by multiple epigenetic mechanisms, including regulation by microRNAs. In this study, microRNA expression profile was investigated in Treg cells isolated from peripheral blood (PB) and from pancreatic draining lymph nodes (PLN) of T1D patients and non-diabetic subjects...
July 31, 2017: Scientific Reports
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