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https://www.readbyqxmd.com/read/28929188/differential-modulation-of-il-12-family-cytokines-in-autoimmune-islet-graft-failure-in-mice
#1
Feng-Cheng Chou, Heng-Yi Chen, Hsin-Hui Chen, Gu-Jiun Lin, Shih-Hua Lin, Huey-Kang Sytwu
AIMS/HYPOTHESIS: The relative contribution of T helper (Th)1 and Th17 cells in graft rejection is inconclusive, on the basis of evidence provided by different T cell-related cytokine-deficient animal models and graft types. METHODS: We used novel antigen-presenting-cell-specific Il-12p35 (also known as Il12a)-knockout (KO), IL-23p19-knockdown (KD) and IL-27p28-KD strategies to investigate T cell differentiation in islet graft rejection. RESULTS: In vitro dendritic cell-T cell coculture experiments revealed that dendritic cells from Il-12p35-KO and IL-23p19-KD mice showed reduced ability to stimulate IFN-γ and IL-17 production in T cells, respectively...
September 19, 2017: Diabetologia
https://www.readbyqxmd.com/read/28928397/atorvastatin-but-not-pravastatin-impairs-mitochondrial-function-in-human-pancreatic-islets-and-rat-%C3%AE-cells-direct-effect-of-oxidative-stress
#2
Francesca Urbano, Marco Bugliani, Agnese Filippello, Alessandra Scamporrino, Stefania Di Mauro, Antonino Di Pino, Roberto Scicali, Davide Noto, Agata Maria Rabuazzo, Maurizio Averna, Piero Marchetti, Francesco Purrello, Salvatore Piro
Statins are a class of drugs widely prescribed as frontline therapy for lowering plasma LDL-cholesterol in cardiovascular risk prevention. Several clinical reports have recently suggested an increased risk of type 2 diabetes associated with chronic use of these drugs. The pathophysiology of this effect remains to be fully elucidated but impaired β-cell function constitutes a potential mechanism. The aim of this study was to explore the effect of a chronic treatment with lipophilic and hydrophilic statins on β-cell function, using human pancreatic islets and rat insulin-secreting INS-1 cells; we particularly focused on the role of mitochondria and oxidative stress...
September 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28924486/expression-of-transcription-factors-in-men1-associated-pancreatic-neuroendocrine-tumors
#3
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/28921392/resveratrol-attenuates-high-glucose-induced-endothelial-cell-apoptosis-via-mediation-of-store-operated-calcium-entry
#4
Ting Lu, Dayan Zhou, Pan Gao, Liangyi Si, Qiang Xu
The aim of this study was to evaluate the influence of resveratrol on HG-induced calcium entry in islet microvascular (MS-1) endothelial cells. MS-1 cells were pretreated with resveratrol or 2-APB (an inhibitor of store-operated calcium entry) and then incubated with high glucose. Cell viability was determined using the cell counting kit-8 method. Reactive oxygen species, endothelial apoptosis, and NO production were detected by DHE probe, TUNEL detection, and nitrate reductase assay kit. Protein levels of SOCE were detected by western blotting...
September 18, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28919263/single-cell-gene-expression-analysis-of-a-human-esc-model-of-pancreatic-endocrine-development-reveals-different-paths-to-%C3%AE-cell-differentiation
#5
Maja Borup Kjær Petersen, Ajuna Azad, Camilla Ingvorsen, Katja Hess, Mattias Hansson, Anne Grapin-Botton, Christian Honoré
The production of insulin-producing β cells from human embryonic stem cells (hESCs) in vitro represents a promising strategy for a cell-based therapy for type 1 diabetes mellitus. To explore the cellular heterogeneity and temporal progression of endocrine progenitors and their progeny, we performed single-cell qPCR on more than 500 cells across several stages of in vitro differentiation of hESCs and compared them with human islets. We reveal distinct subpopulations along the endocrine differentiation path and an early lineage bifurcation toward either polyhormonal cells or β-like cells...
September 8, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28918509/effects-of-tetramethylpyrazine-phosphate-on-pancreatic-islet-microcirculation-in-sd-rats
#6
X Xu, L Wu, Z Q Lu, P Xia, X P Zhu, X Gao
PURPOSES: Abnormal islet microcirculation impetus the insulin production and accelerates progression of Type 1 and 2 diabetes. In this study, we investigated whether tetramethylpyrazine phosphate (TMPP), a vasoactive substance, could regulate the islet microcirculation and insulin concentration and improve glycaemia in SD rats. METHODS: SD rats were randomly divided into two groups, the control and TMPP groups. Each group was further divided into three subgroups according to the intravenous injection of either saline, 15 or 30% glucose...
September 16, 2017: Journal of Endocrinological Investigation
https://www.readbyqxmd.com/read/28911206/identification-of-the-molecular-dysfunction-caused-by-glutamate-dehydrogenase-s445l-mutation-responsible-for-hyperinsulinism-hyperammonemia
#7
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/28911142/deficient-endogenous-glucose-production-during-exercise-after-total-pancreatectomy-islet-autotransplantation
#8
Lindsey D Bogachus, Elizabeth Oseid, Melena Bellin, Adrian Vella, R Paul Robertson
Context: Total pancreatectomy followed by intrahepatic islet autotransplantation (TP/IAT) is performed to alleviate severe, unrelenting abdominal pain caused by chronic pancreatitis, to improve quality of life, and to prevent diabetes. Objective: To determine the cause of exercise-induced hypoglycemia that is a common complaint in TP/IAT recipients. Design: Participants completed 1 hour of steady-state exercise. Setting: Hospital research unit...
September 1, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28901971/xenotransplantation-past-present-and-future
#9
Burcin Ekser, Ping Li, David K C Cooper
PURPOSE OF REVIEW: To review the progress in the field of xenotransplantation with special attention to most recent encouraging findings which will eventually bring xenotransplantation to the clinic in the near future. RECENT FINDINGS: Starting from early 2000, with the introduction of galactose-α1,3-galactose (Gal)-knockout pigs, prolonged survival especially in heart and kidney xenotransplantation was recorded. However, remaining antibody barriers to non-Gal antigens continue to be the hurdle to overcome...
September 8, 2017: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/28887564/inhibition-of-y1-receptor-signaling-improves-islet-transplant-outcome
#10
Kim Loh, Yan-Chuan Shi, Stacey Walters, Mohammed Bensellam, Kailun Lee, Katsuya Dezaki, Masanori Nakata, Chi Kin Ip, Jeng Yie Chan, Esteban N Gurzov, Helen E Thomas, Michaela Waibel, James Cantley, Thomas W Kay, Toshihiko Yada, D Ross Laybutt, Shane T Grey, Herbert Herzog
Failure to secrete sufficient quantities of insulin is a pathological feature of type-1 and type-2 diabetes, and also reduces the success of islet cell transplantation. Here we demonstrate that Y1 receptor signaling inhibits insulin release in β-cells, and show that this can be pharmacologically exploited to boost insulin secretion. Transplanting islets with Y1 receptor deficiency accelerates the normalization of hyperglycemia in chemically induced diabetic recipient mice, which can also be achieved by short-term pharmacological blockade of Y1 receptors in transplanted mouse and human islets...
September 8, 2017: Nature Communications
https://www.readbyqxmd.com/read/28880546/transcriptomic-and-functional-analyses-on-the-effects-of-dioxin-on-insulin-secretion-of-pancreatic-islets-and-%C3%AE-cells
#11
Keng Po Lai, Hin Ting Wan, Alice Hoi-Man Ng, Jing Woei Li, Ting Fung Chan, Chris Kong-Chu Wong
In this study, transcriptomic and Ingenuity Pathway Analysis (IPA) underlined that an ex-vivo TCDD treatment (0.1 nM) stimulated insulin-release in mouse pancreatic islets via the effect on the Akt-mTOR-p70S6K, AMPK and ERK1/2 pathways. Functional studies using both ex-vivo islets and the mouse β-cell-line (Min-6) validated the stimulatory effects of TCDD (0.1 and 1 nM) on basal-insulin secretion. At 0.1 nM TCDD treatment on Min-6, Western blot analysis showed activation of ERK1/2 and decreased expression of pyruvate dehydrogenase kinase (PDK)...
September 21, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/28878738/overlooked-mechanisms-in-type-1-diabetes-etiology-how-unique-costimulatory-molecules-contribute-to-diabetogenesis
#12
REVIEW
David H Wagner
Type 1 Diabetes (T1D) develops when immune cells invade the pancreatic islets resulting in loss of insulin production in beta cells. T cells have been proven to be central players in that process. What is surprising, however, is that classic mechanisms of tolerance cannot explain diabetogenesis; alternate mechanisms must now be considered. T cell receptor (TCR) revision is the process whereby T cells in the periphery alter TCR expression, outside the safety-net of thymic selection pressures. This process results in an expanded T cell repertoire, capable of responding to a universe of pathogens, but limitations are that increased risk for autoimmune disease development occurs...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28877460/persistence-of-pancreatic-insulin-mrna-expression-and-proinsulin-protein-in-type-1-diabetes-pancreata
#13
Clive Wasserfall, Harry S Nick, Martha Campbell-Thompson, Dawn Beachy, Leena Haataja, Irina Kusmartseva, Amanda Posgai, Maria Beery, Christopher Rhodes, Ezio Bonifacio, Peter Arvan, Mark Atkinson
The canonical notion that type 1 diabetes (T1D) results following a complete destruction of β cells has recently been questioned as small amounts of C-peptide are detectable in patients with long-standing disease. We analyzed protein and gene expression levels for proinsulin, insulin, C-peptide, and islet amyloid polypeptide within pancreatic tissues from T1D, autoantibody positive (Ab+), and control organs. Insulin and C-peptide levels were low to undetectable in extracts from the T1D cohort; however, proinsulin and INS mRNA were detected in the majority of T1D pancreata...
September 5, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28863367/monomeric-cocoa-catechins-enhance-%C3%AE-cell-function-by-increasing-mitochondrial-respiration
#14
Thomas J Rowley, Benjamin F Bitner, Jason D Ray, Daniel R Lathen, Andrew T Smithson, Blake W Dallon, Chase J Plowman, Benjamin T Bikman, Jason M Hansen, Melanie R Dorenkott, Katheryn M Goodrich, Liyun Ye, Sean F O'Keefe, Andrew P Neilson, Jeffery S Tessem
A hallmark of type 2 diabetes (T2D) is β-cell dysfunction and the eventual loss of functional β-cell mass. Therefore, mechanisms that improve or preserve β-cell function could be used to improve the quality of life of individuals with T2D. Studies have shown that monomeric, oligomeric and polymeric cocoa flavanols have different effects on obesity, insulin resistance and glucose tolerance. We hypothesized that these cocoa flavanols may have beneficial effects on β-cell function. INS-1 832/13-derived β-cells and primary rat islets cultured with a monomeric catechin-rich cocoa flavanol fraction demonstrated enhanced glucose-stimulated insulin secretion, while cells cultured with total cocoa extract and with oligomeric or polymeric procyanidin-rich fraction demonstrated no improvement...
July 27, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28855611/co-encapsulation-and-co-transplantation-of-mesenchymal-stem-cells-reduces-pericapsular-fibrosis-and-improves-encapsulated-islet-survival-and-function-when-allografted
#15
Vijayaganapathy Vaithilingam, Margaret D M Evans, Denise M Lewy, Penelope A Bean, Sumeet Bal, Bernard E Tuch
Pericapsular fibrotic overgrowth (PFO) is associated with poor survival of encapsulated islets. A strategy to combat PFO is the use of mesenchymal stem cells (MSC). MSC have anti-inflammatory properties and their potential can be enhanced by stimulation with proinflammatory cytokines. This study investigated whether co-encapsulation or co-transplantation of MSC with encapsulated islets would reduce PFO and improve graft survival. Stimulating MSC with a cytokine cocktail of IFN-γ and TNF-α enhanced their immunosuppressive potential by increasing nitric oxide production and secreting higher levels of immunomodulatory cytokines...
August 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28843667/the-specific-localization-of-advanced-glycation-end-products-ages-in-rat-pancreatic-islets
#16
Yuta Morioka, Kiyoshi Teshigawara, Yasuko Tomono, Dengli Wang, Yasuhisa Izushi, Hidenori Wake, Keyue Liu, Hideo Kohka Takahashi, Shuji Mori, Masahiro Nishibori
Advanced glycation end-products (AGEs) are produced by non-enzymatic glycation between protein and reducing sugar such as glucose. Although glyceraldehyde-derived AGEs (Glycer-AGEs), one of the AGEs subspecies, have been reported to be involved in the pathogenesis of various age-relating diseases such as diabetes mellitus or arteriosclerosis, little is known about the pathological and physiological mechanism of AGEs in vivo. In present study, we produced 4 kinds of polyclonal antibodies against AGEs subspecies and investigated the localization of AGEs-modified proteins in rat peripheral tissues, making use of these antibodies...
August 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28842702/stigmasterol-prevents-glucolipotoxicity-induced-defects-in-glucose-stimulated-insulin-secretion
#17
Meliza G Ward, Ge Li, Valéria C Barbosa-Lorenzi, Mingming Hao
Type 2 diabetes results from defects in both insulin sensitivity and insulin secretion. Elevated cholesterol content within pancreatic β-cells has been shown to reduce β-cell function and increase β-cell apoptosis. Hyperglycemia and dyslipidemia contribute to glucolipotoxicity that leads to type 2 diabetes. Here we examined the capacity of glucolipotoxicity to induce free cholesterol accumulation in human pancreatic islets and the INS-1 insulinoma cell line. Glucolipotoxicity treatment increased free cholesterol in β-cells, which was accompanied by increased reactive oxygen species (ROS) production and decreased insulin secretion...
August 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28842399/inhibition-of-12-15-lipoxygenase-protects-against-%C3%AE-cell-oxidative-stress-and-glycemic-deterioration-in-mouse-models-of-type-1-diabetes
#18
Marimar Hernandez-Perez, Gaurav Chopra, Jonathan Fine, Abass M Conteh, Ryan M Anderson, Amelia K Linnemann, Chanelle Benjamin, Jennifer B Nelson, Kara S Benninger, Jerry L Nadler, David J Maloney, Sarah A Tersey, Raghavendra G Mirmira
Islet β-cell dysfunction and aggressive macrophage activity are early features in the pathogenesis of type 1 diabetes (T1D). 12/15-lipoxygenase (12/15-LOX) is induced in β cells and macrophages during T1D and produces pro-inflammatory lipids and lipid peroxides that exacerbate β-cell dysfunction and macrophage activity. Inhibition of 12/15-LOX provides a potential therapeutic approach to prevent glycemic deterioration in T1D. Two inhibitors recently identified by our groups through screening efforts, ML127 and ML351, have been shown to selectively target 12/15-LOX with high potency...
August 25, 2017: Diabetes
https://www.readbyqxmd.com/read/28839233/optogenetic-regulation-of-insulin-secretion-in-pancreatic-%C3%AE-cells
#19
Fan Zhang, Emmanuel S Tzanakakis
Pancreatic β-cell insulin production is orchestrated by a complex circuitry involving intracellular elements including cyclic AMP (cAMP). Tackling aberrations in glucose-stimulated insulin release such as in diabetes with pharmacological agents, which boost the secretory capacity of β-cells, is linked to adverse side effects. We hypothesized that a photoactivatable adenylyl cyclase (PAC) can be employed to modulate cAMP in β-cells with light thereby enhancing insulin secretion. To that end, the PAC gene from Beggiatoa (bPAC) was delivered to β-cells...
August 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28835141/transplantation-of-stromal-derived-factor-1%C3%AE-and-basic-fibroblast-growth-factor-primed-insulin-producing-cells-reverses-hyperglycaemia-in-diabetic-rats
#20
Muhammad Sohail Anjum, Azra Mehmood, Muhammad Ali, Hira Butt, Shaheen N Khan, Sheikh Riazuddin
The defective insulin production is associated with severely reduced islet cell mass leading to diabetes. Growth factors preconditioned stem cells have arisen as an effective therapy to treat many diseases including diabetes. The current study was designed to assess the effect of pretreatment of ASCs derived IPCs with combination of stromal cell derived factor 1 alpha (SDF1α) and basic fibroblast growth factor (bFGF) in improving glucose tolerance in streptozotocin induced diabetic rats. The results showed maximally significant reduction in hyperglycaemia and fibrosis, while up-regulation of survival and pancreas-specific genes, insulin levels and homing of transplanted cells in SDF-1α + bFGF IPCs transplanted rats as compared with other groups...
August 24, 2017: Growth Factors
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