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Anika Sahr, Carmen Wolke, Jonas Maczewsky, Peter Krippeit-Drews, Anja Tetzner, Gisela Drews, Simone Venz, Sarah Gürtler, Jens van den Brandt, Sabine Berg, Paula Döring, Frank Dombrowski, Thomas Walther, Uwe Lendeckel
The ACE2/angiotensin (Ang)-(1-7)/Mas axis of the renin-angiotensin system (RAS) often opposes the detrimental effects of the ACE/AngII/AT1 axis and has been associated with beneficial effects on glucose homeostasis, while underlying mechanisms are mostly unknown. Here, we investigate the effects of Ang-(1-7) and its receptor Mas on β-cell function. Isolated islets from Mas-deficient and wild-type mice were stimulated with Ang-(1-7) or its antagonists and effects on insulin secretion determined. Islets' cytoplasmic calcium and cAMP concentrations, mRNA amounts of Ins1, Ins2, Pdx1, and Mafa, and effects of inhibitors of cAMP downstream signaling were determined...
October 7, 2016: Endocrinology
Hye Seung Jung, Yu Mi Kang, Ho Seon Park, Byung Yong Ahn, Hakmo Lee, Min Joo Kim, Jin Young Jang, Sun-Whe Kim
Post-translational modification by bonding of small ubiquitin-like modifier (SUMO) peptides influences various cellular functions, and is regulated by SUMO-specific proteases (SENPs). Several proteins have been suggested to have diverse impact on insulin synthesis and secretion through SUMO modification in beta cells. However, the role of SUMO modification in beta cell mass has not been established. Here, we examined the changes in expression of Senp in INS1 cells and pancreatic islets under diabetes-relevant stress conditions and associated changes in beta cell mass...
September 20, 2016: Islets
Song Lee, Seonghee Jeong, Chanmi Lee, Jooyun Oh, Song-Cheol Kim
Mesenchymal stem cells (MSCs) derived from bone marrow, adipose tissue, and most connective tissues have been recognized as promising sources for cell-based therapies. MSCs have also been detected in human pancreatic tissue, including endocrine and exocrine cells. These adult human pancreas-derived MSCs have generated a great deal of interest owing to their potential use in the differentiation of insulin-producing cells for diabetes treatment. In the present study, we isolated MSCs from the adult human exocrine pancreas to determine whether isolated MSCs have the potential to differentiate into pancreatic endocrine cells and, therefore, whether they can be used in stem cell-based therapies...
2016: Stem Cells International
Junping Wen, Ting Xue, Ying Huang, Xiaoyan Chen, Ying Xue, Wei Lin, Lizhen Zhang, Jin Yao, Huibin Huang, Jixing Liang, Liantao Li, Lixiang Lin, Lidan Shi, Liangchun Cai, Zhuangli Zhu, Gang Chen
BACKGROUND: Beta-cells in different stages have different function and capacity of proliferation, regenerative and apoptosis. We conducted this study to investigate whether there are changes in beta-cell phonotype in the development of diabetes to identify potential beta cell targets for preventing the progression of diabetes. METHODS: We conducted a cross-sectional study of pancreatic tissues obtained from 80 patients classified into three groups: 25 type2 diabetes, 25 impaired fasting glucose, and 30 non-diabetes...
September 10, 2016: Journal of Diabetes
Shumaila Usman, Irfan Khan, Nadia Naeem, Hana'a Iqbal, Anwar Ali, Sehrish Usman, Asmat Salim
AIM: The study was carried out to evaluate the role of preconditioning strategies on the trans-differentiation of mature fibroblasts (NIH3T3 cells) into insulin producing β-cells. METHODS: The NIH3T3 cells were treated with dexamethasone (5μM) and pancreatic extract (0.05 and 0.4mg/mL) separately or in combination. The treated cells were analyzed for the morphological changes, and expression of pancreatic genes and proteins by phase contrast microscopy, RT-PCR and flow cytometry/immunocytochemistry, respectively...
September 1, 2016: Life Sciences
Ja Young Kim-Muller, Jason Fan, Young Jung R Kim, Seung-Ah Lee, Emi Ishida, William S Blaner, Domenico Accili
Insulin-producing β cells become dedifferentiated during diabetes progression. An impaired ability to select substrates for oxidative phosphorylation, or metabolic inflexibility, initiates progression from β-cell dysfunction to β-cell dedifferentiation. The identification of pathways involved in dedifferentiation may provide clues to its reversal. Here we isolate and functionally characterize failing β cells from various experimental models of diabetes and report a striking enrichment in the expression of aldehyde dehydrogenase 1 isoform A3 (ALDH(+)) as β cells become dedifferentiated...
2016: Nature Communications
Zhenping Liu, Per B Jeppesen, Søren Gregersen, Lotte Bach Larsen, Kjeld Hermansen
BACKGROUND: Pancreatic islet-cell dysfunction is a hallmark in the development of diabetes, but the reasons for the primary β-cell defect are still elusive. Elevated circulating proline levels have been found in subjects with insulin resistance, obesity, and type 2 diabetes. Therefore, we assessed β-cell function, gene expressions, and cell death after long-term exposure of pancreatic β-cells to excess proline in vitro. METHODS: Isolated mouse islets and INS-1E cells were incubated with and without excess proline...
2016: Review of Diabetic Studies: RDS
Yong-Gun Kim, Minjung Kim, Ji Hyun Kang, Hyo Jeong Kim, Jin-Woo Park, Jae-Mok Lee, Jo-Young Suh, Jae-Young Kim, Jae-Hyung Lee, Youngkyun Lee
BACKGROUND: Periodontitis is the most common chronic inflammatory disease caused by complex interaction between the microbial biofilm and host immune responses. In the present study, high-throughput RNA sequencing was utilized to systemically and precisely identify gene expression profiles and alternative splicing. METHODS: The pooled RNAs of 10 gingival tissues from both healthy and periodontitis patients were analyzed by deep sequencing followed by computational annotation and quantification of mRNA structures...
2016: Human Genomics
Dina H Kassem, Mohamed M Kamal, Abd El-Latif G El-Kholy, Hala O El-Mesallamy
BACKGROUND: Diabetes mellitus is a devastating metabolic disease. Generation of insulin-producing cells (IPCs) from stem cells, especially from Wharton's jelly mesenchymal stem cells (WJ-MSCs), has sparked much interest recently. Exendin-4 has several beneficial effects on MSCs and β cells. However, its effects on generation of IPCs from WJ-MSCs specifically have not been studied adequately. The purpose of this study was therefore to investigate how exendin-4 could affect the differentiation outcome of WJ-MSCs into IPCs, and to investigate the role played by exendin-4 in this differentiation process...
2016: Stem Cell Research & Therapy
Nicolò Celadon, Strahinja Došen, Iris Binder, Paolo Ariano, Dario Farina
BACKGROUND: The importance to restore the hand function following an injury/disease of the nervous system led to the development of novel rehabilitation interventions. Surface electromyography can be used to create a user-driven control of a rehabilitation robot, in which the subject needs to engage actively, by using spared voluntary activation to trigger the assistance of the robot. METHODS: The study investigated methods for the selective estimation of individual finger movements from high-density surface electromyographic signals (HD-sEMG) with minimal interference between movements of other fingers...
2016: Journal of Neuroengineering and Rehabilitation
Elisa Corritore, Yong-Syu Lee, Valentina Pasquale, Daniela Liberati, Mei-Ju Hsu, Catherine Anne Lombard, Patrick Van Der Smissen, Amedeo Vetere, Susan Bonner-Weir, Lorenzo Piemonti, Etienne Sokal, Philippe Lysy
: : β-cell replacement therapy represents the most promising approach to restore β-cell mass and glucose homeostasis in patients with type 1 diabetes. Safety and ethical issues associated with pluripotent stem cells stimulated the search for adult progenitor cells with endocrine differentiation capacities. We have already described a model for expansion and differentiation of human pancreatic duct-derived cells (HDDCs) into insulin-producing cells. Here we show an innovative and robust in vitro system for large-scale production of β-like cells from HDDCs using a nonintegrative RNA-based reprogramming technique...
July 12, 2016: Stem Cells Translational Medicine
W Wang, Y-E Lu, M Zhuo, F Ling
We report here the identification of one Mafa-DPA1 and four Mafa-DQB1 novel alleles of Vietnamese cynomolgus macaques.
July 2016: HLA
Adi Sasson, Eleonor Rachi, Lina Sakhneny, Daria Baer, Michal Lisnyansky, Alona Epshtein, Limor Landsman
β-Cells rely on the islet microenvironment for their functionality and mass. Pericytes, along with endothelial cells, make up the dense islet capillary network. However, although the role of endothelial cells in supporting β-cell homeostasis has been vastly investigated, the role of pericytes remains largely unknown. Here, we focus on contribution of pericytes to β-cell function. To this end, we used a transgenic mouse system that allows diphtheria toxin-based depletion of pericytes. Our results indicate that islets depleted of their pericytes have reduced insulin content and expression...
October 2016: Diabetes
Kiyoto Nishi, Yuichi Sato, Mikiko Ohno, Yoshinori Hiraoka, Sayaka Saijo, Jiro Sakamoto, Po-Min Chen, Yusuke Morita, Shintaro Matsuda, Kanako Iwasaki, Kazu Sugizaki, Norio Harada, Yoshiko Mukumoto, Hiroshi Kiyonari, Kenichiro Furuyama, Yoshiya Kawaguchi, Shinji Uemoto, Toru Kita, Nobuya Inagaki, Takeshi Kimura, Eiichiro Nishi
Type 2 diabetes (T2D) is associated with pancreatic β-cell dysfunction, manifested by reduced glucose-stimulated insulin secretion (GSIS). Several transcription factors enriched in β-cells, such as MafA, control β-cell function by organizing genes involved in GSIS. Here we demonstrate that nardilysin (N-arginine dibasic convertase; Nrd1 and NRDc) critically regulates β-cell function through MafA. Nrd1(-/-) mice showed glucose intolerance and severely decreased GSIS. Islets isolated from Nrd1(-/-) mice exhibited reduced insulin content and impaired GSIS in vitro...
October 2016: Diabetes
Zahra Azizi, Claudia Lange, Federico Paroni, Amin Ardestani, Anke Meyer, Yonghua Wu, Axel R Zander, Christof Westenfelder, Kathrin Maedler
Bone marrow mesenchymal stromal cells (MSC) have anti-inflammatory, anti-apoptotic and immunosuppressive properties and are a potent source for cell therapy. Cell fusion has been proposed for rapid generation of functional new reprogrammed cells. In this study, we aimed to establish a fusion protocol of bone marrow-derived human MSCs with the rat beta-cell line (INS-1E) as well as human isolated pancreatic islets in order to generate insulin producing beta-MSCs as a cell-based treatment for diabetes.Human eGFP+ puromycin+ MSCs were co-cultured with either stably mCherry-expressing rat INS-1E cells or human dispersed islet cells and treated with phytohemagglutinin (PHA-P) and polyethylene glycol (PEG) to induce fusion...
June 21, 2016: Oncotarget
Hideaki Kaneto, Atsushi Obata, Masashi Shimoda, Tomohiko Kimura, Hidenori Hirukawa, Seizo Okauchi, Taka-Aki Matsuoka, Kohei Kaku
Pancreatic β-cell dysfunction and insulin resistance are the main characteristics of type 2 diabetes. Chronic exposure of β-cells to hyperglycemia leads to the deterioration of b-cell function. Such phenomena are well known as pancreatic β-cell glucose toxicity. MafA, a strong transactivator of insulin gene, is particularly important for the maintenance of mature β -cell function, but its expression level is significantly reduced under diabetic conditions which is likely associated with β -cell failure...
June 26, 2016: Current Medicinal Chemistry
Parker Lyng Andersen, Patrick Vermette
Current methods of monitoring insulin in culture are limited to soluble insulin (secretions or lysates) or synthetic gene reporter analyses. We present an insulin-specific cell enzyme-linked immunosorbent assay (cell-ELISA) to assess relative intracellular insulin protein content of adherent cultures, normalized to cell density with further immunocytochemical verification of insulin-expressing cells within identical cultures. The protocol was optimized and validated using an insulin-expressing cell line (INS-1) by confirming direct relations between intracellular insulin content and insulin-expressing cell density, in a glucose exposure-dependent manner...
September 10, 2016: Experimental Cell Research
M Nagaya, H Matsunari, T Kanai, M Maehara, K Nakano, I Umeki, Y Katsumata, Y Kasai, R Sakai, M Kobayashi, M Honda, N Abe, M Watanabe, K Umeyama, H Nagashima
The present study aimed at establishing a new cryopreservation method for mouse pancreatic islets by vitrification using hollow fibers as a container. A unique feature of the hollow fiber vitrification (HFV) method is that this method achieves stable vitrification using a minimum volume of cryoprotectant (CPA) solution, thereby ensuring high viability of the islets. The cytotoxicity, optimum composition, and concentration of the CPAs for vitrifying islets were examined. The viability, functional-integrity of vitrified islets were evaluated in comparison with those vitrified by conventional methods...
August 2016: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
Maria J Lima, Kenneth R Muir, Hilary M Docherty, Neil W A McGowan, Shareen Forbes, Yves Heremans, Harry Heimberg, John Casey, Kevin Docherty
Transcription factor mediated lineage reprogramming of human pancreatic exocrine tissue could conceivably provide an unlimited supply of islets for transplantation in the treatment of diabetes. Exocrine tissue can be efficiently reprogrammed to islet-like cells using a cocktail of transcription factors: Pdx1, Ngn3, MafA and Pax4 in combination with growth factors. We show here that overexpression of exogenous Pax4 in combination with suppression of the endogenous transcription factor ARX considerably enhances the production of functional insulin-secreting β-like cells with concomitant suppression of α-cells...
2016: PloS One
Lin Zhang, Wei Chen, Yuee Dai, Ziyang Zhu, Qianqi Liu
Intrauterine growth retardation (IUGR) is a disorder that can result in permanent changes in the physiology and metabolism of the newborn, which increased the risk of disease in adulthood. Evidence supports IUGR as a risk factor for the development of diabetes mellitus, which could reflect changes in pancreas developmental pathways. We sought to characterize the IUGR-induced alterations of the complex pathways of pancreas development in a rat model of IUGR. We analyzed the pancreases of Sprague Dawley rats after inducing IUGR by feeding a maternal low calorie diet from gestational day 1 until term...
July 2016: Experimental Biology and Medicine
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