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Pancreatic beta cells

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https://www.readbyqxmd.com/read/28820316/cell-cycle-related-metabolism-and-mitochondrial-dynamics-in-a-replication-competent-pancreatic-beta-cell-line
#1
Chiara Montemurro, Suryakiran Vadrevu, Tatyana Gurlo, Alexandra E Butler, Kenny E Vongbunyong, Anton Petcherski, Orian S Shirihai, Leslie S Satin, Daniel Braas, Peter C Butler, Slavica Tudzarova
Cell replication is a fundamental attribute of growth and repair in multicellular organisms. Pancreatic beta-cells in adults rarely enter cell cycle, hindering the capacity for regeneration in diabetes. Efforts to drive beta-cells into cell cycle have so far largely focused on regulatory molecules such as cyclins and cyclin-dependent kinases (CDKs). Investigations in cancer biology have uncovered that adaptive changes in metabolism, the mitochondrial network, and cellular Ca(2+) are critical for permitting cells to progress through the cell cycle...
August 18, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28812213/heterogeneity-in-the-beta-cell-population-a-guided-search-into-its-significance-in-pancreas-and-in-implants
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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/28789815/bioprinting-and-cellular-therapies-for-type-1-diabetes
#8
REVIEW
Dino J Ravnic, Ashley N Leberfinger, Ibrahim T Ozbolat
Type 1 diabetes mellitus is a chronic autoimmune disease that results from the destruction of beta (β) cells in the pancreatic islets, leading to loss of insulin production and resultant hyperglycemia. Recent developments in stem cell biology have generated much excitement for β-cell replacement strategies; β cells are one of many cell types in the complex islet environment and pancreas. In this Opinion, we discuss recent successful attempts to generate β cells and how this can be coupled with bioprinting technologies in order to fabricate pancreas tissues, which holds great potential for type 1 diabetes...
August 5, 2017: Trends in Biotechnology
https://www.readbyqxmd.com/read/28775287/non-invasive-in-vivo-determination-of-viable-islet-graft-volume-by-111-in-exendin-3
#9
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
#10
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
#11
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/28767692/insulin-receptor-signaling-and-glucagon-like-peptide-1-effects-on-pancreatic-beta-cells
#12
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/28764929/inhibition-of-aurora-kinase-a-induces-necroptosis-in-pancreatic-carcinoma
#13
Yangchun Xie, Shan Zhu, Meizuo Zhong, Minghua Yang, Xiaofan Sun, Jinbao Liu, Guido Kroemer, Michael Lotze, Herbert J Zeh, Rui Kang, Daolin Tang
BACKGROUND & AIMS: Induction of non-apoptotic cell death could be an approach to eliminate apoptosis-resistant tumors. We investigated necroptosis-based therapies in mouse models of pancreatic ductal adenocarcinoma cancer (PDAC). METHODS: We screened 273 commercially available kinase inhibitors for cytotoxicity against a human PDAC cell line (PANC1). We evaluated the ability of the aurora kinase inhibitor CCT137690 to stimulate necroptosis in PDAC cell lines (PANC1, PANC2...
July 29, 2017: Gastroenterology
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
#14
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
https://www.readbyqxmd.com/read/28760782/cdk4-6-inhibition-on-glucose-and-pancreatic-beta-cell-homeostasis-in-young-and-aged-rats
#15
Aida I Sacaan, Stephane Thibault, Miyoun Hong, Nagesha G Kondegowda, Timothy C Nichols, Rosemary Li, Carolina Rosselot, Winston Evering, Rafael Fenutria, Allison Vitsky, Thomas Brown, Martin B Finkelstein, Adolfo Garcia-Ocaña, Nasir K Khan, Andrew F Stewart, Rupangi C Vasavada
Genetic deletion of cyclin-dependent kinase 4 (CDK4) is associated with pancreatic beta cell loss and glucose dysregulation in rodents. Palbociclib, one of the first selective CDK4/6 inhibitors approved for the treatment of advanced breast cancer, is currently being investigated as an adjuvant treatment in patients with early-stage breast cancer and in a variety of cancers covering a wide-range of patient populations. Hence, longer chronic toxicity studies were necessary to further examine its safety profile...
July 31, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28759009/ginseng-extract-reduces-tacrolimus-induced-oxidative-stress-by-modulating-autophagy-in-pancreatic-beta-cells
#16
Sun Woo Lim, Long Jin, Kang Luo, Jian Jin, Chul Woo Yang
We previously reported that long-term treatment with a calcineurin inhibitor impairs autophagy process in pancreatic beta cells. This study investigated the effect of Korean red ginseng extract (KRGE) on autophagy modulated by oxidative stress. In mice with tacrolimus (Tac)-induced diabetes mellitus, KRGE alleviated islet dysfunction and decreased oxidative stress and autophagic vacuoles. In vitro, KRGE decreased autophagosome formation and attenuated lysosomal degradation, accompanied by improved beta cell viability and insulin secretion...
July 31, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28755631/upregulation-of-ucp2-in-beta-cells-confers-partial-protection-against-both-oxidative-stress-and-glucotoxicity
#17
Ning Li, Melis Karaca, Pierre Maechler
Deterioration of pancreatic beta-cells plays a critical role in the development of type 2 diabetes. Among the various stressors contributing to these deleterious effects, glucotoxicity and superoxides have been proposed as major players. In this context, the mitochondrial uncoupling protein UCP2 is regularly associated with the stress response. In the present study, we tested the effects of UCP2 upregulation in mouse islets with beta-cell specific overexpression of UCP2 (RIP-UCP2). Islets were subjected to both chronic glucotoxicity (7 days at 30mM glucose) and acute oxidative stress (200µM H2O2 for 10min)...
July 21, 2017: Redox Biology
https://www.readbyqxmd.com/read/28754856/overexpression-of-mir-135b-5p-promotes-unfavorable-clinical-characteristics-and-poor-prognosis-via-the-repression-of-sfrp4-in-pancreatic-cancer
#18
Xu Han, Hexige Saiyin, Junjie Zhao, Yuan Fang, Yefei Rong, Chenye Shi, Wenhui Lou, Tiantao Kuang
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive and malignant neoplasm. The aberrant expression of miR-135b-5p and secreted frizzled-related protein 4 (SFRP4) has been revealed to be involved in various cancers. However, the clinical significance of miR-135b-5p and that of its potential target SFRP4 in PDAC remain to be elucidated. Here, we found that miR-135b-5p was markedly upregulated in pancreatic cancer tissue compared with corresponding adjacent normal tissue, whereas SFRP4 was significantly downregulated...
July 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28754804/fifteen-minute-consultation-monogenic-forms-of-diabetes-with-onset-after-age-6-months
#19
Emma M Dyer, Rakesh Amin
Monogenic forms of diabetes (historically known as Maturity Onset Diabetes of the Young (MODY)) are caused by single gene mutations inherited in an autosomal dominant fashion that result in reduced pancreatic beta cell function. Children with these forms of diabetes may be misdiagnosed as having type 1 or 2 diabetes, which has important implications for treatment, genetic counselling, screening of family members and prognosis. Useful tools now exist to aid in their diagnosis and management. Here, we attempt to outline the clinical features that will help the physician make the differentiation from other diabetes subtypes...
July 28, 2017: Archives of Disease in Childhood. Education and Practice Edition
https://www.readbyqxmd.com/read/28754350/beneficial-metabolic-effects-of-dietary-epigallocatechin-gallate-alone-and-in-combination-with-exendin-4-in-high-fat-diabetic-mice
#20
Nupur M Pathak, Paul J B Millar, Varun Pathak, Peter R Flatt, Victor A Gault
OBJECTIVE: Significant attempts are being made to generate multifunctional, hybrid or peptide combinations as novel therapeutic strategies for type 2 diabetes, however this presents key challenges including design and pharmaceutical development. In this study, we evaluated metabolic properties of oral nutritional supplement epigallocatechin gallate (EGCG) in combination with GLP-1 agonist exendin-4 in a mouse model of dietary-induced diabetes and obesity. METHODS: EGCG, exendin-4 or combination of both were administered twice-daily over 28 days to high fat (HF) mice on background of low-dose streptozotocin...
July 25, 2017: Molecular and Cellular Endocrinology
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