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https://www.readbyqxmd.com/read/29775636/epithelial-proliferation-in-inflammatory-skin-disease-is-regulated-by-ttc7-in-fibroblasts-and-lymphocytes
#1
Ursina Nüesch, Andrea A Mauracher, Lennart Opitz, Benjamin Volkmer, Katarzyna Michalak-Mićka, Jivko Kamarachev, Tom Hartwig, Ernst Reichmann, Burkhard Becher, Stefano Vavassori, Jana Pachlopnik Schmid
BACKGROUND: Mutations in tetratricopeptide repeat domain 7A (TTC7A) and its mouse orthologue Ttc7 result in a multisystemic disease, mostly affecting epithelial barriers and the immune system. Despite successful hematopoietic stem cell transplantation, ongoing progression of gastrointestinal manifestations can be life-threatening in TTC7A-deficient patients. OBJECTIVE: To identify whether TTC7A mutations dysregulate epithelial cells only, or whether a cell-intrinsic defect in lymphocytes or other cells contributes to disease manifestations...
May 15, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29773871/the-somatostatin-secreting-pancreatic-%C3%AE-cell-in-health-and-disease
#2
REVIEW
Patrik Rorsman, Mark O Huising
The somatostatin-secreting δ-cells comprise ~5% of the cells of the pancreatic islets. The δ-cells have complex morphology and might interact with many more islet cells than suggested by their low numbers. δ-Cells contain ATP-sensitive potassium channels, which open at low levels of glucose but close when glucose is elevated. This closure initiates membrane depolarization and electrical activity and increased somatostatin secretion. Factors released by neighbouring α-cells or β-cells amplify the glucose-induced effects on somatostatin secretion from δ-cells, which act locally within the islets as paracrine or autocrine inhibitors of insulin, glucagon and somatostatin secretion...
May 17, 2018: Nature Reviews. Endocrinology
https://www.readbyqxmd.com/read/29773801/lrrc8-vrac-anion-channels-enhance-%C3%AE-cell-glucose-sensing-and-insulin-secretion
#3
Till Stuhlmann, Rosa Planells-Cases, Thomas J Jentsch
Glucose homeostasis depends critically on insulin that is secreted by pancreatic β-cells. Serum glucose, which is directly sensed by β-cells, stimulates depolarization- and Ca2+ -dependent exocytosis of insulin granules. Here we show that pancreatic islets prominently express LRRC8A and LRRC8D, subunits of volume-regulated VRAC anion channels. Hypotonicity- or glucose-induced β-cell swelling elicits canonical LRRC8A-dependent VRAC currents that depolarize β-cells to an extent that causes electrical excitation...
May 17, 2018: Nature Communications
https://www.readbyqxmd.com/read/29773001/combined-administration-of-monosodium-glutamate-and-high-sucrose-diet-accelerates-the-induction-of-type-2-diabetes-vascular-dysfunction-and-memory-impairment-in-rats
#4
Kaja Saikrishna, Ringu Kumari, Kantamaneni Chaitanya, Subhankar Biswas, Pawan G Nayak, Jayesh Mudgal, Anoop Kishore, Krishnadas Nandakumar
In this study, we aimed to develop an experimental animal model for type 2 diabetes mellitus (T2DM) using a combination of monosodium glutamate (MSG) and high sucrose diet (HSD). Young male Wistar rats (20-30 g) were injected with MSG (2 or 4 mg/g, i.p. for 4 days). These rats were also fed an HSD, while the control group was fed a starch diet (SFD) for 150 days. Parameters assessed periodically were body weight, feed intake, blood glucose level, and oral glucose tolerance test (OGTT), lipid profile, liver and kidney function tests, skeletal muscle glucose uptake, cognitive function tests, and microvascular changes using isolated rat aorta...
2018: Journal of Environmental Pathology, Toxicology and Oncology
https://www.readbyqxmd.com/read/29771768/high-density-infiltration-of-v-domain-immunoglobulin-suppressor-of-t-cell-activation-up-regulated-immune-cells-in-human-pancreatic-cancer
#5
Jinʼe Liu, Xiaoxue Xie, Chunxiao Xuan, Tingting Li, Lanlan Wang, Lianghong Teng, Jun Liu
V-domain immunoglobulin suppressor of T-cell activation (VISTA) is constitutively expressed in hematopoietic lineage and is highly up-regulated in tumor infiltrated myeloid cells and regulatory T cells in animal models. However, its expression in human pancreatic tumor microenvironment remains unknown. In this research, we aimed at the expression of VISTA in human pancreatic cancer samples. METHODS: We performed immunohistochemistry to determine VISTA expression in human pancreatic cancer samples...
May 15, 2018: Pancreas
https://www.readbyqxmd.com/read/29771178/islet-microvasculature-alterations-with-loss-of-beta-cells-in-patients-with-type-1-diabetes
#6
Joseph S Canzano, Lith H Nasif, Elizabeth A Butterworth, Dongtao A Fu, Mark A Atkinson, Martha Campbell-Thompson
Islet microvasculature provides key architectural and functional roles, yet the morphological features of islets from patients with type 1 diabetes are poorly defined. We examined islet and exocrine microvasculature networks by multiplex immunofluorescence imaging of pancreases from organ donors with and without type 1 diabetes ( n=17 and n=16, respectively) and determined vessel diameter, density, and area. We also analyzed these variables in insulin-positive and insulin-negative islets of 7 type 1 diabetes donors...
May 1, 2018: Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society
https://www.readbyqxmd.com/read/29770600/how-does-glucagon-like-peptide-1-stimulate-human-%C3%AE-cell-proliferation-a-lesson-from-islet-graft-experiments
#7
Yoshio Fujitani
The incidence of type 2 diabetes increases with age. The age-dependent decline in functional β-cell mass contributes to the increased risk of onset of diabetes, reflecting the central role of pancreatic β cells in glucose homeostasis. Indeed, the replication rate of human and rodent β cells is known to decline sharply with age, and such a characteristic of β cells may explain the increased onset of type 2 diabetes in the older population. The molecular mechanism involved in the age-dependent decline of β-cell proliferation has been extensively studied, mainly using rodents and in vitro culture systems, but its molecular basis is still largely unknown...
May 16, 2018: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/29770308/allo-and-auto-percutaneous-intra-portal-pancreatic-islet-transplantation-pipit-for-diabetes-cure-and-prevention-the-role-of-imaging-and-interventional-radiology
#8
REVIEW
Massimo Venturini, Claudio Sallemi, Paolo Marra, Anna Palmisano, Giulia Agostini, Carolina Lanza, Gianpaolo Balzano, Massimo Falconi, Antonio Secchi, Paolo Fiorina, Lorenzo Piemonti, Paola Maffi, Antonio Esposito, Francesco De Cobelli, Alessandro Del Maschio
Although the life expectancy of patients with type 1 diabetes mellitus (T1DM) has improved since the introduction of insulin therapy, the acute life-threatening and long-term complications from diabetes mellitus are significant causes of both mortality and morbidity. Percutaneous intra-portal pancreatic islet transplantation (PIPIT) is a minimally invasive, repeatable procedure which allows a β-cell replacement therapy through a liver islet engraftment, leading to insulin release and glycaemic control restoration in patients with diabetes...
April 2018: Gland Surgery
https://www.readbyqxmd.com/read/29770221/risperidone-induced-type-2-diabetes-presenting-with-diabetic-ketoacidosis
#9
Clarissa Ern Hui Fang, Mohammed Faraz Rafey, Aine Cunningham, Sean F Dinneen, Francis M Finucane
A 28-year-old male presented with 2 days of vomiting and abdominal pain, preceded by 2 weeks of thirst, polyuria and polydipsia. He had recently started risperidone for obsessive-compulsive disorder. He reported a high dietary sugar intake and had a strong family history of type 2 diabetes mellitus (T2DM). On admission, he was tachycardic, tachypnoeic and drowsy with a Glasgow Coma Scale (GCS) of 10/15. We noted axillary acanthosis nigricans and obesity (BMI 33.2 kg/m2 ). Dipstick urinalysis showed ketonuria and glycosuria...
2018: Endocrinology, Diabetes & Metabolism Case Reports
https://www.readbyqxmd.com/read/29769672/pancreas-regeneration
#10
REVIEW
Qiao Zhou, Douglas A Melton
The pancreas is made from two distinct components: the exocrine pancreas, a reservoir of digestive enzymes, and the endocrine islets, the source of the vital metabolic hormone insulin. Human islets possess limited regenerative ability; loss of islet β-cells in diseases such as type 1 diabetes requires therapeutic intervention. The leading strategy for restoration of β-cell mass is through the generation and transplantation of new β-cells derived from human pluripotent stem cells. Other approaches include stimulating endogenous β-cell proliferation, reprogramming non-β-cells to β-like cells, and harvesting islets from genetically engineered animals...
May 2018: Nature
https://www.readbyqxmd.com/read/29769449/fatty-acid-receptor-modulator-pbi-4050-inhibits-kidney-fibrosis-and-improves-glycemic-control
#11
Yan Li, Sungjin Chung, Zhilian Li, Jessica M Overstreet, Lyne Gagnon, Brigitte Grouix, Martin Leduc, Pierre Laurin, Ming-Zhi Zhang, Raymond C Harris
Extensive kidney fibrosis occurs in several types of chronic kidney diseases. PBI-4050, a potentially novel first-in-class orally active low-molecular weight compound, has antifibrotic and antiinflammatory properties. We examined whether PBI-4050 affected the progression of diabetic nephropathy (DN) in a mouse model of accelerated type 2 diabetes and in a model of selective tubulointerstitial fibrosis. eNOS-/- db/db mice were treated with PBI-4050 from 8-20 weeks of age (early treatment) or from 16-24 weeks of age (late treatment)...
May 17, 2018: JCI Insight
https://www.readbyqxmd.com/read/29767012/corrigendum-to-the-role-of-costimulation-blockade-in-solid-organ-and-islet-xenotransplantation
#12
Kannan P Samy, James R Butler, Ping Li, David K C Cooper, Burcin Ekser
[This corrects the article DOI: 10.1155/2017/8415205.].
2018: Journal of Immunology Research
https://www.readbyqxmd.com/read/29765322/therapeutic-potential-of-ginsenosides-as-an-adjuvant-treatment-for-diabetes
#13
REVIEW
Litao Bai, Jialiang Gao, Fan Wei, Jing Zhao, Danwei Wang, Junping Wei
Ginseng, one of the oldest traditional Chinese medicinal herbs, has been used widely in China and Asia for thousands of years. Ginsenosides extracted from ginseng, which is derived from the roots and rhizomes of Panax ginseng C. A. Meyer, have been used in China as an adjuvant in the treatment of diabetes mellitus. Owing to the technical complexity of ginsenoside production, the total ginsenosides are generally extracted. Accumulating evidence has shown that ginsenosides exert antidiabetic effects. In vivo and in vitro tests revealed the potential of ginsenoside Rg1, Rg3, Rg5, Rb1, Rb2, Rb3, compound K, Rk1, Re, ginseng total saponins, malonyl ginsenosides, Rd, Rh2, F2, protopanaxadiol (PPD) and protopanaxatriol (PPT)-type saponins to treat diabetes and its complications, including type 1 diabetes mellitus, type 2 diabetes mellitus, diabetic nephropathy, diabetic cognitive dysfunction, type 2 diabetes mellitus with fatty liver disease, diabetic cerebral infarction, diabetic cardiomyopathy, and diabetic erectile dysfunction...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29759973/enhanced-glucose-control-following-vertical-sleeve-gastrectomy-does-not-require-a-%C3%AE-cell-glucagon-like-peptide-1-receptor
#14
Jonathan D Douros, Alfor G Lewis, Eric P Smith, JingJing Niu, Megan Capozzi, April Wittmann, Jonathan Campbell, Jenny Tong, Constance Wagner, Parinaz Mahbod, Randy Seeley, David A D'Alessio
Bariatric surgeries, including vertical sleeve gastrectomy (VSG), resolve diabetes in 40-50% of patients. Studies examining the molecular mechanisms underlying this effect have centered on the role of the insulinotropic glucagon-like peptide 1 (GLP-1), in great part because of the ∼10-fold rise in its circulating levels after surgery. However, there is currently debate over the role of direct β-cell signaling by GLP-1 to mediate improved glucose tolerance following surgery. In order to assess the importance of β-cell GLP-1 receptor (GLP-1R) for improving glucose control after VSG, a mouse model of this procedure was developed and combined with a genetically modified mouse line allowing an inducible, β-cell specific Glp1r knockdown ( Glp1r β-cell-ko )...
May 14, 2018: Diabetes
https://www.readbyqxmd.com/read/29758481/kaempferol-alleviates-palmitic-acid-induced-lipid-stores-endoplasmic-reticulum-stress-and-pancreatic-%C3%AE-cell-dysfunction-through-ampk-mtor-mediated-lipophagy
#15
Ritu Varshney, Rajat Varshney, Rutusmita Mishra, Sumeet Gupta, Debabrata Sircar, Partha Roy
Kaempferol, a natural flavonoid, has the beneficial effects of preserving pancreatic β-cell mass and function, but its action on β-cell lipid metabolism still remains elusive. Recently, autophagy has been reported to play a major role in lipid metabolism in various cell types, but its role in pancreatic β-cell's lipid metabolism is rarely reported. Here, we investigated the role of kaempferol-induced autophagy in inhibition of lipid stores, ER stress and β-cell dysfunction in palmitic acid-challenged RIN-5F cells and isolated pancreatic islets...
March 2, 2018: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/29758224/humanised-recombinant-antibody-fragments-bind-human-pancreatic-islet-cells
#16
Abigail C Buenafe, Philip R Streeter
We describe here the humanisation of two mouse monoclonal antibodies that bind to surface markers on human pancreatic islet endocrine cells. Monoclonal antibodies produced by the HIC1-2B4 and HIC0-4F9 mouse hybridomas bind distinct surface molecules expressed on endocrine cells and have been validated for a number of experimental methods including immunohistochemistry and live cell sorting by flow cytometry. Variable region framework and first constant region domain sequences were replaced with that from compatible human antibody sequences, and the resulting recombinant antigen-binding fragments were cloned and expressed in mouse myeloma cells...
May 11, 2018: Journal of Immunological Methods
https://www.readbyqxmd.com/read/29758169/nutritional-recovery-from-low-protein-diet-during-pregnancy-does-not-restore-the-kinetics-of-insulin-secretion-and-ca2-or-alterations-in-the-camp-pka-and-plc-pkc-pathways-in-islets-from-adult-rats
#17
Leonardo Marin, Hellen Barbosa Farias Silva, Gabriela Damin, Leticia Martins Ignacio-Souza, Silvia Regina de Lima Reis, Camila Aparecida Machado de Oliveira, Rosane Aparecida Ribeiro, Marise A Reis, Marcia Queiroz Latorraca, Fabiano Ferreira, Vanessa Cristina Arantes
We investigated the insulin release induced by glucose, the Ca2+ oscillatory pattern and the cAMP/PKA and PLC/PKC pathways in islets from adult rats that were reared under diets with 17% protein (C) or 6% protein (LP) during gestation, suckling and after weaning and in rats receiving diets with 6% protein during gestation, followed by a 17% protein diet after birth (R). Glucose-induced first-phase insulin secretion was reduced in LP and R islets, and the second phase was partially restored in the R group. Glucose stimulation did not modify [Ca2+]i, but it reduced the [Ca2+] oscillatory frequency in the R group compared to the C group...
May 14, 2018: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
https://www.readbyqxmd.com/read/29757902/differential-impact-of-t-bet-and-ifn%C3%AE-on-pancreatic-islet-allograft-rejection
#18
Alix Besançon, Zeynep Demir, Tania Goncalves, Fabrice Valette, Emilie Panafieu, Lucienne Chatenoud, Sylvaine You
BACKGROUND: T-cell-mediated graft rejection is mostly correlated with potent Th1 responses. However, since IFNγ mice reject their graft as efficiently as wild-type (WT) mice, the exact contribution of IFNγ and its transcription factor T-bet remains a matter of debate. Here, we address this question in the context of pancreatic islet allograft to better inform the molecular pathways that hampers islet survival in vivo. METHODS: Pancreatic islets from BALB/c mice were transplanted in WT, IFNγ or T-bet C57BL/6 mice...
May 2, 2018: Transplantation
https://www.readbyqxmd.com/read/29757700/adhesion-characteristics-of-porcine-pancreatic-islets-and-exocrine-tissue-to-coating-materials
#19
Yoshiki Nakashima, Chika Miyagi-Shiohira, Naoya Kobayashi, Issei Saitoh, Masami Watanabe, Hirofumi Noguchi
Since the report of the Edmonton protocol in 2000, islet transplantation has been implemented worldwide, and xenotransplantation using porcine islets has also been reported. In addition, many basic experiments using pancreatic islets and exocrine tissue after isolation have been reported. Recently, exocrine cells have been found to be essential for inducing the differentiation of pancreatic islets. Therefore, the importance of the culture conditions for pancreatic tissue when conducting experiments using pancreatic tissue is also increasing...
May 14, 2018: Islets
https://www.readbyqxmd.com/read/29757200/a-rationally-designed-hsp70-variant-rescues-the-aggregation-associated-toxicity-of-human-iapp-in-cultured-pancreatic-islet-%C3%AE-cells
#20
Marie Nicole Bongiovanni, Francesco Antonio Aprile, Pietro Sormanni, Michele Vendruscolo
Molecular chaperones are key components of the protein homeostasis system against protein misfolding and aggregation. It has been recently shown that these molecules can be rationally modified to have an enhanced activity against specific amyloidogenic substrates. The resulting molecular chaperone variants can be effective inhibitors of protein aggregation in vitro, thus suggesting that they may provide novel opportunities in biomedical and biotechnological applications. Before such opportunities can be exploited, however, their effects on cell viability should be better characterised...
May 12, 2018: International Journal of Molecular Sciences
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