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https://www.readbyqxmd.com/read/28544245/ghrelin-receptor-inverse-agonists-as-a-novel-therapeutic-approach-against-obesity-related-metabolic-disease
#1
Kathrin Abegg, Lara Bernasconi, Melanie Hutter, Lynda Whiting, Claudio Pietra, Claudio Giuliano, Thomas A Lutz, Thomas Riediger
AIMS: Ghrelin is implicated in the control of energy balance and glucose homeostasis. The ghrelin receptor exhibits ligand independent constitutive activity, which can be pharmacologically exploited to induce inverse ghrelin actions. Since ghrelin receptor inverse agonists (GHSR-IA) might be effective for the treatment of obesity-related metabolic disease, we tested two novel synthetic compounds GHSR-IA1 and GHSR-IA2. MATERIALS AND METHODS: In functional cell assays, electrophysiogical and immunohistochemical experiments, we demonstrated inverse agonist activity for GHSR-IA1 and GHSR-IA2...
May 24, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28544229/clinical-heterogeneity-of-type-1-diabetes-t1d-found-in-asia
#2
REVIEW
Yongsoo Park, Kupper A Wintergerst, Zhiguang Zhou
Diabetes mellitus among young patients in Asia is caused by a complex set of factors. Although T1D remains the most common form of diabetes in children, the recent unabated increase in obesity has resulted in the emergence of T2D as a new type of diabetes at adolescent and young adult age. In addition to the typical autoimmune type 1 diabetes (T1aD) and type 2 diabetes (T2D) patients, there is a variable incidence of cases of non-autoimmune types of T1D associated with insulin deficiency (T1bD). Additional forms have been described, including fulminant T1D (FT1D)...
May 19, 2017: Diabetes/metabolism Research and Reviews
https://www.readbyqxmd.com/read/28542568/nesfatin-1-like-peptide-is-a-novel-metabolic-factor-that-suppresses-feeding-and-regulates-whole-body-energy-homeostasis-in-male-wistar-rats
#3
Kavishankar Gawli, Naresh Ramesh, Suraj Unniappan
Nucleobindin-1 has high sequence similarity to nucleobindin-2, which encodes the anorectic and metabolic peptide, nesfatin-1. We previously reported a nesfatin-1-like peptide (NLP), anorectic in fish and insulinotropic in mice islet beta-like cells. The main objective of this research was to determine whether NLP is a metabolic regulator in male Wistar rats. A single intraperitoneal (IP) injection of NLP (100 μg/kg BW) decreased food intake and increased ambulatory movement, without causing any change in total activity or energy expenditure when compared to saline-treated rats...
2017: PloS One
https://www.readbyqxmd.com/read/28542303/differential-dna-methylation-of-msi2-and-its-correlation-with-diabetic-traits
#4
Jae-Pil Jeon, In-Uk Koh, Nak-Hyun Choi, Bong-Jo Kim, Bok-Ghee Han, Suman Lee
Differential DNA methylation with hyperglycemia is significantly associated with Type 2 Diabetes (T2D). Longtime extended exposure to high blood glucose levels can affect the epigenetic signatures in all organs. However, the relevance of the differential DNA methylation changes with hyperglycemia in blood with pancreatic islets remains unclear. We investigated differential DNA methylation in relation to glucose homeostasis based on the Oral Glucose Tolerance Test (OGTT) in a population-based cohort. We found a total of 382 differential methylation sites from blood DNA in hyperglycemia and type 2 diabetes subgroups using a longitudinal and cross-sectional approach...
2017: PloS One
https://www.readbyqxmd.com/read/28542222/differential-expression-of-islet-glutaredoxin-1-and-5-with-high-reactive-oxygen-species-production-in-a-mouse-model-of-diabesity
#5
Sebastian Friedrich Petry, Fatemeh Sharifpanah, Heinrich Sauer, Thomas Linn
The onset and progression of diabetes mellitus type 2 is highly contingent on the amount of functional beta-cell mass. An underlying cause of beta-cell decay in diabetes is oxidative stress, which markedly affects the insulin producing pancreatic cells due to their poor antioxidant defence capacity. Consequently, disturbances of cellular redox signaling have been implicated to play a major role in beta-cell loss in diabetes mellitus type 2. There is evidence suggesting that the glutaredoxin (Grx) system exerts a protective role for pancreatic islets, but the exact mechanisms have not yet been elucidated...
2017: PloS One
https://www.readbyqxmd.com/read/28542139/regulator-of-g-protein-signaling-2-is-a-key-regulator-of-pancreatic-%C3%AE-cell-mass-and-function
#6
H Dong, Y Zhang, J Wang, D S Kim, H Wu, B Sjögren, W Gao, L Luttrell, H Wang
Pancreatic β-cell death and dysfunction contributes to the pathogenesis of both type 1 and type 2 diabetes. We aimed to examine whether the regulator of G protein signaling protein 2 (RGS2), a multifunctional inhibitor of G protein-coupled receptor (GPCR) signaling, impacts β-cell death and function. Metabolic phenotypes, β-cell secretory function, and glucose and insulin tolerance were measured in RGS2 knockout (RGS2(-/-)) mice and their wild-type (RGS2(+/+)) littermate controls. β-Cell death was evaluated in RGS2-knockdown and -overexpressing β cells and RGS2(-/-) islets by flow cytometry, western blot, ELISA, TUNEL staining, and apoptosis RT(2) profiler PCR array analysis...
May 25, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28540469/a-3d-microfluidic-perfusion-system-made-from-glass-for-multiparametric-analysis-of-stimulus-secretioncoupling-in-pancreatic-islets
#7
Torben Schulze, Kai Mattern, Eike Früh, Lars Hecht, Ingo Rustenbeck, Andreas Dietzel
Microfluidic perfusion systems (MPS) are well suited to perform multiparametric measurements with small amounts of tissue to function as an Organ on Chip device (OOC). Such microphysiolgical characterization is particularly valuable in research on the stimulus-secretion-coupling of pancreatic islets. Pancreatic islets are fully functional competent mini-organs, which serve as fuel sensors and transduce metabolic activity into rates of hormone secretion. To enable the simultaneous measurement of fluorescence and oxygen consumption we designed a microfluidic perfusion system from borosilicate glass by 3D femtosecond laser ablation...
September 2017: Biomedical Microdevices
https://www.readbyqxmd.com/read/28539593/identification-of-the-matricellular-protein-fibulin-5-as-a-target-molecule-of-glucokinase-mediated-calcineurin-nfat-signaling-in-pancreatic-islets
#8
Tomoko Okuyama, Jun Shirakawa, Hiromi Yanagisawa, Mayu Kyohara, Shunsuke Yamazaki, Kazuki Tajima, Yu Togashi, Yasuo Terauchi
Glucokinase-mediated glucose signaling induces insulin secretion, proliferation, and apoptosis in pancreatic β-cells. However, the precise molecular mechanisms underlying these processes are not clearly understood. Here, we demonstrated that glucokinase activation using a glucokinase activator (GKA) significantly upregulated the expression of Fibulin-5 (Fbln5), a matricellular protein involved in matrix-cell signaling, in isolated mouse islets. The islet Fbln5 expression was induced by ambient glucose in a time- and dose-dependent manner and further enhanced by high-fat diet or the deletion of insulin receptor substrate 2 (IRS-2), whereas the GKA-induced increase in Fbln5 expression was diminished in Irs-2-deficient islets...
May 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28539272/selenium-nanoparticles-as-versatile-carriers-for-oral-delivery-of-insulin-insight-into-the-synergic-antidiabetic-effect-and-mechanism
#9
Wenji Deng, Qian Xie, Huan Wang, Zhiguo Ma, Baojian Wu, Xingwang Zhang
Oral insulin delivery has been plagued by limited bioavailability. This work reports selenium nanoparticles (SeNPs) for oral insulin delivery to overcome the absorption barrier. Insulin-loaded SeNPs (INS-SeNPs) were fabricated by ionic cross-linking/in situ reduction and characterized by particle size and drug entrapment. The resultant INS-SeNPs were 120nm around in particle size with high drug loading. INS-SeNPs exhibited controllable insulin release and outstanding stability in the digestive fluids. INS-SeNPs caused a significant hypoglycemic effect in both normal and diabetic rats...
May 21, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/28535085/characterization-of-an-encapsulated-insulin-secreting-human-pancreatic-beta-cell-line-in-a-modular-microfluidic-device
#10
Argia Acarregui, Jesús Ciriza, Laura Saenz Del Burgo, Haritz Gurruchaga, José Yeste, Xavier Illa, Gorka Orive, Rosa M Hernández, Rosa Villa, Jose Luis Pedraz
Type I diabetes mellitus is characterized by the destruction of the insulin producing beta cells within the pancreas by the immune system. After the success of Edmonton protocol, islet transplantation has shown to be a promising therapy, but with the Achilles´ heel of the need of using immunosuppressive drugs. Currently, cell encapsulation technology represents a real alternative to protect transplanted islets from the host´s immune attack. Although preliminary in vitro studies with encapsulated cells have been traditionally performed under static conditions in terms of viability and efficiency, these static cultures do not represent a close approach to in vivo environments...
May 23, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/28534310/combination-immunotherapy-for-type-1-diabetes
#11
REVIEW
Robert N Bone, Carmella Evans-Molina
PURPOSE OF REVIEW: Type 1 diabetes (T1D) is an autoimmune disease marked by β-cell destruction. Immunotherapies for T1D have been investigated since the 1980s and have focused on restoration of tolerance, T cell or B cell inhibition, regulatory T cell (Treg) induction, suppression of innate immunity and inflammation, immune system reset, and islet transplantation. The purpose of this review is to provide an overview and lessons learned from single immunotherapy trials, describe recent and ongoing combination immunotherapy trials, and provide perspectives on strategies for future combination clinical interventions aimed at preserving insulin secretion in T1D...
July 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/28533434/lysophosphatidylinositol-induced-activation-of-the-cation-channel-trpv2-triggers-glucagon-like-peptide-1-secretion-in-enteroendocrine-l-cells
#12
Kazuki Harada, Tetsuya Kitaguchi, Taichi Kamiya, Kyaw Htet Aung, Kazuaki Nakamura, Kunihiro Ohta, Takashi Tsuboi
The lysophosphatidylinositol (LPI) has crucial roles in multiple physiological processes, including insulin exocytosis from pancreatic islets. However, the role of LPI in secretion of glucagon like peptide-1 (GLP-1), a hormone that enhances glucose-induced insulin secretion, is unclear. Here, we used the murine enteroendocrine L cell line GLUTag and primary murine small intestinal cells to elucidate the mechanism of LPI-induced GLP-1 secretion. Exogenous LPI addition increased intracellular Ca2+ concentrations ([Ca2+]i) in GLUTag cells and induced GLP-1 secretion from both GLUTag and acutely prepared primary intestinal cells...
May 22, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28533295/comparative-pathogenesis-of-autoimmune-diabetes-in-humans-nod-mice-and-canines-has-a-valuable-animal-model-of-type-1-diabetes-been-overlooked
#13
Allison L O'Kell, Clive Wasserfall, Brian Catchpole, Lucy J Davison, Rebecka S Hess, Jake A Kushner, Mark A Atkinson
Despite decades of research in humans and mouse models of disease, substantial gaps remain in our understanding of pathogenic mechanisms underlying the development of type 1 diabetes. Furthermore, translation of therapies from preclinical efforts capable of delaying or halting β-cell destruction has been limited. Hence, a pressing need exists to identify alternative animal models that reflect human disease. Canine insulin deficiency diabetes is, in some cases, considered to follow autoimmune pathogenesis, similar to NOD mice and humans, characterized by hyperglycemia requiring lifelong exogenous insulin therapy...
June 2017: Diabetes
https://www.readbyqxmd.com/read/28532691/bio-synthetic-materials-for-immunomodulation-of-islet-transplants
#14
Greg A Foster, Andrés J García
Clinical islet transplantation is an effective therapy in restoring physiological glycemic control in type 1 diabetics. However, allogeneic islets derived from cadaveric sources elicit immune responses that result in acute and chronic islet destruction. To prevent immune destruction of islets, transplant recipients require lifelong delivery of immunosuppressive drugs, which are associated with debilitating side effects. Biomaterial-based strategies to eliminate the need for immunosuppressive drugs are an emerging therapy for improving islet transplantation...
May 19, 2017: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/28532102/islet-encapsulated-implantable-composite-hollow-fiber-membrane-based-device-a-bioartificial-pancreas
#15
Rohit S Teotia, Sachin Kadam, Atul Kumar Singh, Surendra Kumar Verma, Ashutosh Bahulekar, Sujata Kanetkar, Jayesh Bellare
Islets from xeno-sources and islet like clusters derived from autologus stem cells have emerged as alternatives to cadaveric pancreas used for treatment of type 1 diabetes. However, the immuno-isolation of these islets from the host immune system suffers from the issue of biocompatibility and hypoxia. To overcome the issues of immunobarrier biocompatibility, we developed a Polysulfone (Psf)/TPGS composite hollow fiber membrane (HFM) using a hollow fiber spinning pilot plant specially developed for this purpose...
August 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28532044/pancreatic-differentiation-of-induced-pluripotent-stem-cells-in-activin-a-grafted-gelatin-poly-lactide-co-glycolide-nanoparticle-scaffolds-with-induction-of-ly294002-and-retinoic-acid
#16
Yung-Chih Kuo, Yu-Chuan Liu, Rajendiran Rajesh
The differentiation of induced pluripotent stem cells (iPSCs) in biomaterial scaffolds is an emerging area for biomedical applications. This study proposes, for the first time, the production of pancreatic cells from iPSCs in gelatin-poly(lactide-co-glycolide) nanoparticle (PLGA NP) scaffolds. The porosity and swelling ratio of the scaffolds decreased with increases in gelatin and PLGA NP concentrations. The adhesion efficiency of iPSCs in gelatin-PLGA NP scaffolds was found to be higher at 6.7% (w/w) PLGA NP...
August 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28529957/abnormal-glucose-metabolism-in-rheumatoid-arthritis
#17
REVIEW
Hui Pi, Haotong Zhou, Huan Jin, Yaogui Ning, Youlian Wang
The incidence of abnormal glucose metabolism in patients with rheumatoid arthritis was considerably higher than the general population. The persistent systemic inflammatory state in rheumatoid arthritis might be associated with the glucose metabolism dysfunction. In this context, insulin resistance, islet β cell apoptosis, inflammatory cytokines, and other aspects which were linked with abnormal glucose metabolism in rheumatoid arthritis were reviewed. This review will be helpful in understanding the abnormal glucose metabolism mechanism in patients with rheumatoid arthritis and might be conducive to finding an effective treatment...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28529277/levels-of-glucose-regulatory-hormones-in-patients-with-non-islet-cell-tumor-hypoglycemia-including-a-review-of-the-literature
#18
Izumi Fukuda, Akira Asai, Tomoko Nagamine, Taro Harada, Kyoko Tanimura-Inagaki, Naomi Hizuka, Hitoshi Sugihara
Non-islet cell tumor hypoglycemia (NICTH) is one of the causes of spontaneous hypoglycemia. The pathogenesis of NICTH is thought to be an excessive production by tumors of big insulin-like growth factor (IGF)-II. This study investigated the levels of glucose-regulatory hormones in patients with NICTH with high serum levels of big IGF-II (big IGF-II group) and compared these with profiles of patients with spontaneous hypoglycemia with normal IGF-II (normal IGF-II group). Circulating IRI, CPR, ACTH, cortisol, GH, and IGF-I levels measured during hypoglycemic episodes were examined retrospectively in 37 patients with big IGF-II producing NICTH and 6 hypoglycemic patients with normal IGF-II...
May 19, 2017: Endocrine Journal
https://www.readbyqxmd.com/read/28528633/correlative-light-electron-microscopy-in-liquid-using%C3%A2-an-inverted-sem-asem
#19
Chikara Sato, Takaaki Kinoshita, Nassirhadjy Memtily, Mari Sato, Shoko Nishihara, Toshiko Yamazawa, Shinya Sugimoto
In atmospheric scanning electron microscope (ASEM), the inverted scanning electron microscope (SEM) observes the wet sample from below, while an optical microscope observes it from above simultaneously. The ASEM sample holder has a disposable dish shape with a silicon nitride film window at the bottom. It can be coated variously for the primary-culture of substrate-sensitive cells; primary cells were cultured in a few milliliters of culture medium in a stable incubator environment. For the inverted SEM observation, cells and the excised tissue blocks were aldehyde-fixed, immersed in radical scavenger solution, and observed at minimum electron dose...
2017: Methods in Cell Biology
https://www.readbyqxmd.com/read/28527919/mechanisms-of-the-amplifying-pathway-of-insulin-secretion-in-the-%C3%AE-cell
#20
REVIEW
Michael A Kalwat, Melanie Cobb
Pancreatic islet β cells secrete insulin in response to nutrient secretagogues, like glucose, dependent on calcium influx and nutrient metabolism. One of the most intriguing qualities of β cells is their ability to use metabolism to amplify the amount of secreted insulin independent of further alterations in intracellular calcium. Many years studying this amplifying process have shaped our current understanding of β cell stimulus-secretion coupling; yet, the exact mechanisms of amplification have been elusive...
May 17, 2017: Pharmacology & Therapeutics
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