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https://www.readbyqxmd.com/read/29341416/resveratrol-influences-pancreatic-islets-by-opposing-effects-on-electrical-activity-and-insulin-release
#1
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/29339498/mafa-missense-mutation-causes-familial-insulinomatosis-and-diabetes-mellitus
#2
Donato Iacovazzo, Sarah E Flanagan, Emily Walker, Rosana Quezado, Fernando Antonio de Sousa Barros, Richard Caswell, Matthew B Johnson, Matthew Wakeling, Michael Brändle, Min Guo, Mary N Dang, Plamena Gabrovska, Bruno Niederle, Emanuel Christ, Stefan Jenni, Bence Sipos, Maike Nieser, Andrea Frilling, Ketan Dhatariya, Philippe Chanson, Wouter W de Herder, Björn Konukiewitz, Günter Klöppel, Roland Stein, Márta Korbonits, Sian Ellard
The β-cell-enriched MAFA transcription factor plays a central role in regulating glucose-stimulated insulin secretion while also demonstrating oncogenic transformation potential in vitro. No disease-causing MAFA variants have been previously described. We investigated a large pedigree with autosomal dominant inheritance of diabetes mellitus or insulinomatosis, an adult-onset condition of recurrent hyperinsulinemic hypoglycemia caused by multiple insulin-secreting neuroendocrine tumors of the pancreas. Using exome sequencing, we identified a missense MAFA mutation (p...
January 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29338697/additional-dexamethasone-in-chemotherapies-with-carboplatin-and-paclitaxel-could-reduce-the-impaired-glycometabolism-in-rat-models
#3
Yanxiu Guo, Haoxia Zeng, Xiaohong Chang, Chaohua Wang, Heng Cui
BACKGROUND: Side-effects have been considered as the limitation of the chemotherapy agents' administration and life quality in patients with ovarian cancers. In order to explore the influence of the chemotherapy agents commonly used in ovarian cancer patients on the blood glucose metabolism in rat models, we conducted this study which simulated the conditions of clinical protocols. METHODS: Eighty clean-grade female Wistar rats were randomized into 8 groups: Group 1 (Negative control), Group 1' (Dexamethasone), Group 2 (Carboplatin), Group 2' (Carboplatin-plus-dexamethasone), Group 3 (Paclitaxel), Group 3' (Paclitaxel-plus-dexamethasone), Group 4 (Combined therapy), Group 4' (Combined-therapy-plus-dexamethasone)...
January 16, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29338388/novel-fusion-protein-targeting-mitochondrial-dna-improves-pancreatic-islet-functional-potency-and-islet-transplantation-outcomes
#4
Juan S Danobeitia, Peter J Chlebeck, Inna Shokolenko, Xiaobo Ma, Glenn Wilson, Luis A Fernandez
Long-term graft survival is an ongoing challenge in the field of islet transplantation. With the growing demand for transplantable organs, therapies to improve organ quality and reduce the incidence of graft dysfunction are of paramount importance. We evaluated the protective role of a recombinant DNA repair protein targeted to mitochondria (Exscien I-III), as a therapeutic agent using a rodent model of pancreatic islet transplantation. We first investigated the effect of therapy on isolated rat islets cultured with pro-inflammatory cytokines (interleukin-1 β, interferon γ, and tumor necrosis factor α) for 48 h and documented a significant reduction in apoptosis by flow cytometry, improved viability by immunofluorescence, and conserved functional potency in vitro and in vivo in Exscien I-III-treated islets...
November 2017: Cell Transplantation
https://www.readbyqxmd.com/read/29338387/quantifying-the-effects-of-different-neutral-proteases-on-human-islet-integrity
#5
Heide Brandhorst, Paul R V Johnson, Olle Korsgren, Daniel Brandhorst
Efficient islet release from the pancreas requires the combination of collagenase, neutral protease (cNP), or thermolysin (TL). Recently, it has been shown that clostripain (CP) may also contribute to efficient islet release from the human pancreas. The aim of this study was to evaluate the impact of these proteases on human islet integrity in a prospective approach. Islets were isolated from the pancreas of 10 brain-dead human organ donors. Purified islets were precultured for 3 to 4 d at 37 °C to ensure that preparations were cleared of predamaged islets, and only integral islets were subjected to 90 min of incubation at 37 °C in Hank's balanced salt solution supplemented with cNP, TL, or CP...
November 2017: Cell Transplantation
https://www.readbyqxmd.com/read/29338381/effect-of-the-diabetic-state-on-islet-engraftment-and-function-in-a-large-animal-model-of-islet-kidney-transplantation
#6
Prashanth Vallabhajosyula, Atsushi Hirakata, Matthew Weiss, Adam Griesemer, Akira Shimizu, Hanzhou Hong, Andreas Habertheuer, Vaja Tchipashvili, Kazuhiko Yamada, David H Sachs
In islet transplantation, in addition to immunologic and ischemic factors, the diabetic/hyperglycemic state of the recipient has been proposed, although not yet validated, as a possible cause of islet toxicity, contributing to islet loss during the engraftment period. Using a miniature swine model of islet transplantation, we have now assessed the effect of a persistent state of hyperglycemia on islet engraftment and subsequent function. An islet-kidney (IK) model previously described by our laboratory was utilized...
November 2017: Cell Transplantation
https://www.readbyqxmd.com/read/29337308/rage-binds-preamyloid-iapp-intermediates-and-mediates-pancreatic-%C3%AE-cell-proteotoxicity
#7
Andisheh Abedini, Ping Cao, Annette Plesner, Jinghua Zhang, Meilun He, Julia Derk, Sachi A Patil, Rosa Rosario, Jacqueline Lonier, Fei Song, Hyunwook Koh, Huilin Li, Daniel P Raleigh, Ann Marie Schmidt
Islet amyloidosis is characterized by the aberrant accumulation of islet amyloid polypeptide (IAPP) in pancreatic islets, resulting in β cell toxicity, which exacerbates type 2 diabetes and islet transplant failure. It is not fully clear how IAPP induces cellular stress or how IAPP-induced toxicity can be prevented or treated. We recently defined the properties of toxic IAPP species. Here, we have identified a receptor-mediated mechanism of islet amyloidosis-induced proteotoxicity. In human diabetic pancreas and in cellular and mouse models of islet amyloidosis, increased expression of the receptor for advanced glycation endproducts (RAGE) correlated with human IAPP-induced (h-IAPP-induced) β cell and islet inflammation, toxicity, and apoptosis...
January 16, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29337137/basal-mitophagy-occurs-independently-of-pink1-in-mouse-tissues-of-high-metabolic-demand
#8
Thomas G McWilliams, Alan R Prescott, Lambert Montava-Garriga, Graeme Ball, François Singh, Erica Barini, Miratul M K Muqit, Simon P Brooks, Ian G Ganley
Dysregulated mitophagy has been linked to Parkinson's disease (PD) due to the role of PTEN-induced kinase 1 (PINK1) in mediating depolarization-induced mitophagy in vitro. Elegant mouse reporters have revealed the pervasive nature of basal mitophagy in vivo, yet the role of PINK1 and tissue metabolic context remains unknown. Using mito-QC, we investigated the contribution of PINK1 to mitophagy in metabolically active tissues. We observed a high degree of mitophagy in neural cells, including PD-relevant mesencephalic dopaminergic neurons and microglia...
January 10, 2018: Cell Metabolism
https://www.readbyqxmd.com/read/29337057/heterogeneity-of-autophagic-status-in-pancreatic-%C3%AE-cells-under-metabolic-stress
#9
Mai Kamitani, Takeshi Miyatsuka, Masaki Miura, Kosuke Azuma, Luka Suzuki, Miwa Himuro, Takehiro Katahira, Yuya Nishida, Yoshio Fujitani, Hirotaka Watada
Autophagy in β cells has been demonstrated to play a pivotal role in cellular homeostasis and the progression of glucose intolerance. Although autophagic activity is affected by metabolic stress both in vivo and in vitro, it remains unclear as to what extent the autophagic status in each β cell is different from its neighboring cells. To address this question, GFP-LC3 reporter mice, which can visualize the autophagic status of each β cell as green-fluorescent puncta, were crossed with obese diabetic db/db mice...
January 11, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29335884/effects-of-moderate-exercise-on-biochemical-morphological-and-physiological-parameters-of-the-pancreas-of-female-mice-with-estrogen-deprivation-and-dyslipidemia
#10
Aparecida Gabriela Bexiga Veloso, Nathalia Edviges Alves Lima, Elisabete de Marco Ornelas, Clever Gomes Cardoso, Mara Rubia Marques, Beatriz da Costa Aguiar Alves Reis, Fernando Luiz Affonso Fonseca, Laura Beatriz Mesiano Maifrino
Menopausal women are at high risk of developing heart disease. However, physical exercise practice can reverse this scenario. We evaluated the biochemical, morphological, and physiological effects of moderate aerobic physical exercise on the pancreas of knockout mice for LDL receptor with estrogen deprivation by ovariectomy. Animals were divided into six groups (n = 5): sedentary non-ovariectomized control; sedentary ovariectomized control; trained ovariectomized control; sedentary non-ovariectomized LDL-R knockout; sedentary ovariectomized LDL-R knockout; and trained ovariectomized LDL-R knockout...
January 15, 2018: Medical Molecular Morphology
https://www.readbyqxmd.com/read/29335487/increased-expression-of-glp-1r-in-proliferating-islets-of-men1-mice-is-detectable-by-68ga-ga-do3a-vs-cys40-exendin-4-pet
#11
Azita Monazzam, Joey Lau, Irina Velikyan, Su-Chen Li, Masoud Razmara, Ulrika Rosenström, Olof Eriksson, Britt Skogseid
Multiple endocrine neoplasia type 1 (MEN1) is an endocrine tumor syndrome caused by heterozygous mutations in the MEN1 tumor suppressor gene. The MEN1 pancreas of the adolescent gene carrier frequently contain diffusely spread pre-neoplasias and microadenomas, progressing to macroscopic and potentially malignant pancreatic neuroendocrine tumors (P-NET), which represents the major death cause in MEN1. The unveiling of the molecular mechanism of P-NET which is not currently understood fully to allow the optimization of diagnostics and treatment...
January 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29333922/effect-of-resveratrol-treatment-on-graft-revascularization-after-islet-transplantation-in-streptozotocin-induced-diabetic-mice
#12
Eun-Mi Lee, Inwon Park, Ye-Jee Lee, Young-Hye You, Ji-Won Kim, Myung-Jun Kim, Yu-Bae Ahn, Pilhan Kim, Seung-Hyun Ko
We evaluated the effect of resveratrol (RSV) on graft survival after islet transplantation (ITx) in diabetic mice. Isolated islets from Balb/c mice (200 IEQ) were transplanted under the kidney capsule of diabetic Balb/c mice. Vehicle or RSV (200 mg/kg/day, orally) was given for 14 days after ITx. Two more control groups [STZ-treated (No-ITx-Control) and STZ+RSV-treated (No-ITx-RSV) mice without ITx] were added. Glucose tolerance tests (GTT) was performed at 14 days after ITx. In vitro, isolated islets pretreated with vehicle or RSV (1 μM) were incubated in a hypoxic chamber (O2 1%, 1hr)...
January 15, 2018: Islets
https://www.readbyqxmd.com/read/29333050/improvement-of-insulin-secretion-and-pancreatic-%C3%AE-cell-function-in-streptozotocin-induced-diabetic-rats-treated-with-aloe-vera-extract
#13
Ayesha Noor, S Gunasekaran, M A Vijayalakshmi
Background: Diabetes mellitus is a metabolic disorder characterized by chronic hyperglycemia. Plant extracts and their products are being used as an alternative system of medicine for the treatment of diabetes. Aloe vera has been traditionally used to treat several diseases and it exhibits antioxidant, anti-inflammatory, and wound-healing effects. Streptozotocin (STZ)-induced Wistar diabetic rats were used in this study to understand the potential protective effect of A. vera extract on the pancreatic islets...
December 2017: Pharmacognosy Research
https://www.readbyqxmd.com/read/29331666/age-related-oxidative-changes-in-pancreatic-islets-are-predominantly-located-in-the-vascular-system
#14
Richard Kehm, Jeannette König, Kerstin Nowotny, Tobias Jung, Stephanie Deubel, Sabrina Gohlke, Tim Julius Schulz, Annika Höhn
Aged tissues usually show a decreased regenerative capacity accompanied by a decline in functionality. During aging pancreatic islets also undergo several morphological and metabolic changes. Besides proliferative and regenerative limitations, endocrine cells lose their secretory capacity, contributing to a decline in functional islet mass and a deregulated glucose homeostasis. This is linked to several features of aging, such as induction of cellular senescence or the formation of modified proteins, such as advanced glycation end products (AGEs) - the latter mainly examined in relation to hyperglycemia and in disease models...
December 29, 2017: Redox Biology
https://www.readbyqxmd.com/read/29331269/clinical-benefits-of-autologous-haematopoietic-stem-cell-transplantation-in-type-1-diabetes-patients
#15
B Gu, H Miao, J Zhang, J Hu, W Zhou, W Gu, W Wang, G Ning
Type 1 diabetes (T1D) is characterized by severe damage to pancreas islet function through immunological attack; therefore, it is also called 'insulin-dependent diabetes'. The present study aimed to evaluate the safety and clinical efficacy of autologous haematopoietic stem cell transplantation (AHSCT) in adolescent patients with newly diagnosed T1D. A phase-II prospective, parallel-assignment, non-randomized trial was conducted from March 2008 to December 2011 with 40 T1D patients, of whom 20 received AHSCT therapy and 20 were treated only with insulin injections...
December 22, 2017: Diabetes & Metabolism
https://www.readbyqxmd.com/read/29330944/improvement-of-islet-function-and-survival-by-integration-of-perfluorodecalin-into-microcapsules-in-vivo-and-in-vitro
#16
Sang-Ho Lee, Heon-Seok Park, Yeoree Yang, Eun-Young Lee, Ji-Won Kim, Gilson Khang, Kun-Ho Yoon
Hypoxic injury of islets is a major obstacle for encapsulated islet transplantation into the peritoneal cavity. To improve oxygen delivery to encapsulated islets, we integrated 20% of the oxygen carrier material, perfluorodecalin (PFD), in alginate capsules mixed with islets (PFD-alginate). Integration of PFD clearly improved islet viability and decreased reactive oxygen species production compared to islets encapsulated with alginate only (alginate) and naked islets exposed to hypoxia in vitro. In PFD-alginate capsules, HIF-1α expression was minimal, and insulin expression was well maintained...
January 12, 2018: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/29330559/a-post-translational-balancing-act-the-good-and-the-bad-of-sumoylation-in-pancreatic-islets
#17
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/29330456/20-hete-promotes-glucose-stimulated-insulin-secretion-in-an-autocrine-manner-through-ffar1
#18
Sorin Tunaru, Remy Bonnavion, Isabell Brandenburger, Jens Preussner, Dominique Thomas, Klaus Scholich, Stefan Offermanns
The long-chain fatty acid receptor FFAR1 is highly expressed in pancreatic β-cells. Synthetic FFAR1 agonists can be used as antidiabetic drugs to promote glucose-stimulated insulin secretion (GSIS). However, the physiological role of FFAR1 in β-cells remains poorly understood. Here we show that 20-HETE activates FFAR1 and promotes GSIS via FFAR1 with higher potency and efficacy than dietary fatty acids such as palmitic, linoleic, and α-linolenic acid. Murine and human β-cells produce 20-HETE, and the ω-hydroxylase-mediated formation and release of 20-HETE is strongly stimulated by glucose...
January 12, 2018: Nature Communications
https://www.readbyqxmd.com/read/29330353/afadin-and-rhoa-control-pancreatic-endocrine-mass-via-lumen-morphogenesis
#19
D Berfin Azizoglu, Caitlin Braitsch, Denise K Marciano, Ondine Cleaver
Proper lumen morphogenesis during pancreas development is critical to endocrine and exocrine cell fate. Recent studies showed that a central network of lumens (termed core), but not the surrounding terminal branches (termed periphery), produces most islet endocrine cells. To date, it remains unclear how pancreatic lumens form and remodel and which aspects of lumen morphogenesis influence cell fate. Importantly, models testing the function of the central lumen network as an endocrine niche are lacking. Here, we identify mechanisms underlying lumen formation and remodeling and show that central lumen network morphogenesis impacts pancreatic endocrine mass...
January 12, 2018: Genes & Development
https://www.readbyqxmd.com/read/29330151/interleukin-22-reverses-human-islet-dysfunction-and-apoptosis-triggered-by-hyperglycemia-and-light
#20
Shadab Abadpour, Bente Halvorsen, Afaf Sahraoui, Olle Korsgren, Pål Aukrust, Hanne Scholz
Interleukin (IL)-22 has recently been suggested as an anti-inflammatory cytokine that could protect the islet cells from inflammation- and glucose-induced toxicity. We have previously shown that the tumor necrosis factor family member, LIGHT can impair human islet function at least partly via pro-apoptotic effects. Herein, we aimed to investigate the protective role of IL-22 on human islets exposed to the combination of hyperglycemia and LIGHT. First, we found up-regulation of LIGHT receptors (LTβR and HVEM) in engrafted human islets exposed to hyperglycemia (>11 mM) for 17 days post transplantation by using a double islet transplantation mouse model as well as in human islets cultured with high glucose (HG) (20mM glucose) + LIGHT in vitro and this latter effect was attenuated by IL-22...
January 12, 2018: Journal of Molecular Endocrinology
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