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Pancreas islet

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https://www.readbyqxmd.com/read/28917147/combined-in-silico-approaches-for-the-identification-of-novel-inhibitors-of-human-islet-amyloid-polypeptide-hiapp-fibrillation
#1
Palak Patel, Krupali Parmar, Vivek K Vyas, Dhaval Patel, Mili Das
Human islet amyloid polypeptide (hIAPP) is a natively unfolded polypeptide hormone of glucose metabolism, which is co-secreted with insulin by the β-cells of the pancreas. In patients with type 2 diabetes, IAPP forms amyloid fibrils because of diabetes-associated β-cells dysfunction and increasing fibrillation, in turn, lead to failure of secretory function of β-cells. This provides a target for the discovery of small organic molecules against protein aggregation diseases. However, the binding mechanism of these molecules with monomers, oligomers and fibrils to inhibit fibrillation is still an open question...
September 6, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28912863/a-novel-mutation-in-the-hepatocyte-nuclear-factor-1%C3%AE-gene-in-maturity-onset-diabetes-of-the-young-5-with-multiple-renal-cysts-and-pancreas-hypogenesis-a-case-report
#2
You Lv, Zhuo Li, Kan He, Ying Gao, Xianchao Xiao, Yujia Liu, Guixia Wang
A 17-year-old Chinese male was hospitalized exhibiting hyperglycemia and increased serum urea nitrogen and creatinine levels in addition to weight loss. The patient was treated with gliclazide. The patient was 150 cm tall, weighed 35 kg and had no family history of diabetes or kidney disease. Physical examination revealed cephalus quadratus, rachitic rosary and a visible toe-out gait. Laboratory examinations revealed that the patient's fasting plasma glucose and glycosylated hemoglobin levels were markedly increased, fasting plasma C-peptide level was slightly increased and no peak 2 h postprandial was observed...
October 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28911868/central-and-peripheral-expression-sites-of-phoenixin-14-immunoreactivity-in-rats
#3
Philip Prinz, Sophie Scharner, Tiemo Friedrich, Martha Schalla, Miriam Goebel-Stengel, Matthias Rose, Andreas Stengel
Phoenixin is a pleiotropic peptide involved in reproduction, anxiety and recently also implicated in the control of food intake. Besides the 20-amino acid phoenixin, the 14-amino acid phoenixin-14 also shows bioactive properties. However, the expression sites of phoenixin-14 in the brain and peripheral tissues are not yet described in detail. Therefore, a mapping of the brain and peripheral tissues from male and female Sprague-Dawley rats with a specific phoenixin-14 antibody was performed using western blot and immunohistochemistry...
September 11, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28905065/be-positive-optimizing-pramlintide-from-microcanonical-analysis-of-amylin-isoforms
#4
Rafael B Frigori
Amylin, or human islet amyloid polypeptide (hIAPP), is a 37-residue hormone synergistic to insulin and co-secreted with it by β-cells in the pancreas. The deposition of its cytotoxic amyloid fibrils is strongly related to the progression of Type II diabetes (T2D) and islet graft failures. Notably, isoforms from some mammalian species, such as rats (rIAPP) and porcine (pIAPP), present a few key mutations preventing aggregation. This has lead to biotechnological development of drugs for adjunct therapies of T2D, such as pramlintide, a variant of hIAPP inspired by rIAPP whose proline substitutions have β-strand fibril-breaking properties...
September 14, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28903914/long-term-treatment-with-the-ghrelin-receptor-antagonist-d-lys3-ghrp-6-does-not-improve-glucose-homeostasis-in-non-obese-diabetic-mkr-mice
#5
Rasha Mosa, Lili Huang, Hongzhuo Li, Michael Grist, Derek LeRoith, Chen Chen
Ghrelin secretion has been associated with increased caloric intake and adiposity. The expressions of ghrelin and its receptor (GHS-R1a) in pancreas have raised the interest about the role of ghrelin in glucose homeostasis. Most of the studies showed that ghrelin promoted hyperglycaemia and inhibited insulin secretion. This raised the interest in using GHS-R1a antagonists as therapeutic targets for type 2 diabetes. Available data of GHS-R antagonists are on a short-term basis. Moreover, the complexity of GHS-R1a signalling makes it difficult to understand the mechanism of action of GHS-R1a antagonists...
September 13, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/28893946/a-radial-axis-defined-by-semaphorin-to-neuropilin-signaling-controls-pancreatic-islet-morphogenesis
#6
Philip T Pauerstein, Krissie Tellez, Kirk B Willmarth, Keon Min Park, Brian Hsueh, H Efsun Arda, Xueying Gu, Haig Aghajanian, Karl Deisseroth, Jonathan A Epstein, Seung K Kim
The islets of Langerhans are endocrine organs characteristically dispersed throughout the pancreas. During development, endocrine progenitors delaminate, migrate radially, and cluster to form islets. Despite the distinctive distribution of islets, spatially localized signals that control islet morphogenesis have not been discovered. Here we identify a radial signaling axis that instructs developing islet cells to disperse throughout the pancreas. A screen of pancreatic extracellular signals identified factors that stimulated islet cell development...
September 11, 2017: Development
https://www.readbyqxmd.com/read/28891030/species-differences-in-pancreatic-binding-of-do3a-vs-cys-40-exendin4
#7
Olof Eriksson, Ulrika Rosenström, Ram K Selvaraju, Barbro Eriksson, Irina Velikyan
AIMS: Radiolabeled Exendin-4 has been proposed as suitable imaging marker for pancreatic beta cell mass quantification mediated by Glucagon-like peptide-1 receptor (GLP-1R). However, noticeable species variations in basal pancreatic uptake as well as uptake reduction degree due to selective beta cell ablation were observed. METHODS: In vitro and ex vivo autoradiography studies of pancreas were performed using [(177)Lu]Lu-DO3A-VS-Cys(40)-Exendin4, in order to investigate the mechanism of uptake as well as the islet uptake contrast in mouse, rat, pig, and non-human primate...
September 11, 2017: Acta Diabetologica
https://www.readbyqxmd.com/read/28889199/oral-delivery-of-staphylococcal-nuclease-by-lactococcus-lactis-prevents-type-1-diabetes-mellitus-in-nod-mice
#8
Junchao Lang, Xiaoke Wang, Kunfeng Liu, Dongmei He, Pancong Niu, Rongyue Cao, Liang Jin, Jie Wu
Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by the self-destruction of insulin-producing β cells. Recently, studies have revealed that neutrophils contribute to the early pathological injury to the pancreas, predominantly via the formation of neutrophil extracellular traps (NETs). To determine whether early intervention targeting NETs with staphylococcal nuclease (SNase) can delay the onset of T1DM, non-obese diabetic (NOD) mice were orally administered recombinant Lactococcus lactis (L...
September 9, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28887612/effect-of-acute-exposure-to-pfoa-on-mouse-liver-cells-in-vivo-and-in-vitro
#9
Xinmou Wu, Minqing Liang, Zhao Yang, Min Su, Bin Yang
Increasingly, epidemiological evidences indicate chemosynthetic perfluorooctanoic acid (PFOA), an environmental pollutant, induces potential adverse effect on human health after long-term exposure. However, less study has been performed for assessment of acute effect of PFOA exposure on metabolic homeostasis. In experimental designs, PFOA-exposed liver cells in vivo and in vitro were used to discuss underlying mechanism related to PFOA-induced metabolic dysfunction. In serological tests, PFOA-exposed mice showed increased treads of liver functional enzymes in alanine transaminase (ALT), aspartate transaminase (AST), and total bilirubin (T-BIL), trypsinase, low density lipoprotein-cholesterol (LDL-C), and insulin, while blood glucose, high density lipoprotein-cholesterol (HDL-C), and glucagon levels were reduced...
September 8, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28885496/%C3%A3-cell-replacement-therapy-the-next-10-years
#10
Christian Schuetz, Takayuki Anazawa, Sarah E Cross, Leticia Labriola, Raphael P H Meier, Robert R Redfield, Hanne Scholz, Peter G Stock, Nathan W Zammit
ß cell replacement with either pancreas or islet transplantation has progressed immensely over the last decades with current 1- and 5-year insulin independence rates of ~85% and ~50%, respectively. Recent advances are largely attributed to improvements in immunosuppressive regimen, donor selection and surgical technique. However, both strategies are compromised by a scarce donor source. Xenotransplantation provides a potential solution by providing a theoretically unlimited supply of islets, but clinical application has been limited by concerns for a potent immune response against xenogeneic tissue...
September 6, 2017: Transplantation
https://www.readbyqxmd.com/read/28884202/gcg-creert2-knockin-mice-as-a-tool-for-genetic-manipulation-in-pancreatic-alpha-cells
#11
Chiyo Shiota, Krishna Prasadan, Ping Guo, Joseph Fusco, Xiangwei Xiao, George K Gittes
AIMS/HYPOTHESIS: The Cre/loxP system, which enables tissue-specific manipulation of genes, is widely used in mice for diabetes research. Our aim was to develop a new Cre-driver mouse line for the specific and efficient manipulation of genes in pancreatic alpha cells. METHODS: A Gcg (CreERT2) knockin mouse, which expresses a tamoxifen-inducible form of Cre from the endogenous preproglucagon (Gcg) gene locus, was generated by homologous recombination. The new Gcg (CreERT2) mouse line was crossed to the Rosa26 (tdTomato) (R26 (tdTomato) ) Cre reporter mouse line in order to evaluate the tissue specificity, efficiency and tamoxifen dependency of Gcg (CreERT2) -mediated recombination...
September 7, 2017: Diabetologia
https://www.readbyqxmd.com/read/28883792/antidiabetic-effect-of-tibetan-medicine-tang-kang-fu-san-in-db-db-mice-via-activation-of-pi3k-akt-and-ampk-pathways
#12
Bailu Duan, Zhongqiu Zhao, Weifang Liao, Hui Xiong, Sisi Liu, Liang Yin, Tiexiang Gao, Zhinan Mei
This study was to investigate the anti-diabetic effects and molecular mechanisms of Tang-Kang-Fu-San (TKFS), a traditional Tibetan medicine, in treating type 2 diabetes mellitus of spontaneous diabetic db/db mice. Firstly HPLC fingerprint analysis was performed to gain the features of the chemical compositions of TKFS. Next different doses of TKFS (0.5 g/kg, 1.0 g/kg, and 2.0 g/kg) were administrated via oral gavage to db/db mice and their controls for 4 weeks. TKFS significantly lowered hyperglycemia and ameliorated insulin resistance (IR) in db/db mice, indicated by results from multiple tests, including fasting blood glucose test, intraperitoneal insulin and glucose tolerance tests, fasting serum insulin levels and homeostasis model assessment of IR analysis as well as histology of pancreas islets...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28878130/an-ancestral-retroviral-protein-identified-as-a-therapeutic-target-in-type-1-diabetes
#13
Sandrine Levet, Julie Medina, Julie Joanou, Amandine Demolder, Nelly Queruel, Kevin Réant, Matthieu Normand, Marine Seffals, Julie Dimier, Raphaële Germi, Thomas Piofczyk, Jacques Portoukalian, Jean-Louis Touraine, Hervé Perron
Human endogenous retroviruses (HERVs), remnants of ancestral viral genomic insertions, are known to represent 8% of the human genome and are associated with several pathologies. In particular, the envelope protein of HERV-W family (HERV-W-Env) has been involved in multiple sclerosis pathogenesis. Investigations to detect HERV-W-Env in a few other autoimmune diseases were negative, except in type-1 diabetes (T1D). In patients suffering from T1D, HERV-W-Env protein was detected in 70% of sera, and its corresponding RNA was detected in 57% of peripheral blood mononuclear cells...
September 7, 2017: JCI Insight
https://www.readbyqxmd.com/read/28877912/type-1-interferons-potentiate-human-cd8-t-cell-cytotoxicity-through-a-stat4-and-granzyme-b-dependent-pathway
#14
Brittney N Newby, Todd M Brusko, Baiming Zou, Mark A Atkinson, Michael Clare-Salzler, Clayton E Mathews
Events defining the progression to human type 1 diabetes (T1D) have remained elusive owing to the complex interaction between genetics, the immune system, and the environment. Type 1 Interferons (T1-IFN) are known to be a constituent of the auto-inflammatory milieu within the pancreas of patients with T1D. However, the capacity of IFNα/β to modulate human activated auto-reactive CD8(+) T cell (CTL) responses within the islets of patients with T1D have not been investigated. Here, we engineer human beta cell specific CTLs and demonstrate that T1-IFN augments cytotoxicity by inducing rapid phosphorylation of STAT4, resulting in direct binding at the granzyme B (GZMB) promoter within 2 hours of exposure...
September 6, 2017: Diabetes
https://www.readbyqxmd.com/read/28877242/comparative-quantitative-proteomic-analysis-of-disease-stratified-laser-captured-microdissected-human-islets-identifies-proteins-and-pathways-potentially-related-to-type-1-diabetes
#15
Julius O Nyalwidhe, Wojciech J Grzesik, Tanya C Burch, Michele L Semeraro, Tayab Waseem, Ivan C Gerling, Raghavendra G Mirmira, Margaret A Morris, Jerry L Nadler
Type 1 diabetes (T1D) is a chronic inflammatory disease that is characterized by autoimmune destruction of insulin-producing pancreatic beta cells. The goal of this study was to identify novel protein signatures that distinguish Islets from patients with T1D, patients who are autoantibody positive without symptoms of diabetes, and from individuals with no evidence of disease. High resolution high mass accuracy label free quantitative mass spectrometry analysis was applied to islets isolated by laser capture microdissection from disease stratified human pancreata from the Network for Pancreatic Organ Donors with Diabetes (nPOD), these included donors without diabetes, donors with T1D-associated autoantibodies in the absence of diabetes, and donors with T1D...
2017: PloS One
https://www.readbyqxmd.com/read/28870071/an-orcein-related-small-molecule-o4-destabilizes-hiapp-protofibrils-by-interacting-mostly-with-the-amyloidogenic-core-region
#16
Yu Zou, Zhenyu Qian, Yunxiang Sun, Guanghong Wei, Qingwen Zhang
The accumulation of the human islet amyloid polypeptide (hIAPP) deposits in the pancreas is regarded as an important factor that leads to the depletion of islet β-cells and islet transplantation failure. Recent experiments reported that small organic molecule O4 inhibits the formation of hIAPP1-37 oligomers and fibrils. However, the interaction between O4 molecules and hIAPP oligomers is largely unknown at atomic level. In this work, we studied the influence of O4 molecules on fibril-like hIAPP pentamer and decamer by performing atomistic molecular dynamics simulations...
September 4, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28867112/pet-computed-tomography-and-precision-medicine-in-pancreatic-adenocarcinoma-and-pancreatic-neuroendocrine-tumors
#17
REVIEW
Daniella F Pinho, Rathan M Subramaniam
(18)F-FDG PET/CT has been described as an accurate tool for initial diagnosis of pancreatic adenocarcinoma. It differentiates benign from malignant causes; detects local and, especially, distant spread of disease; and is a very good predictor of patient prognosis. Pancreatic neuroendocrine tumors are rare tumors that originate from the islet cells of the pancreas. Currently, (68)Ga-DOTA-labeled somatostatin analogs are considered the best modality for detection of well-differentiated neuroendocrine tumors. (18)F-FDG PET/CT has a role in patients with poorly differentiated tumors...
October 2017: PET Clinics
https://www.readbyqxmd.com/read/28865118/glucose-stimulated-insulin-release-parallel-perifusion-studies-of-free-and-hydrogel-encapsulated-human-pancreatic-islets
#18
Peter Buchwald, Alejandro Tamayo-Garcia, Vita Manzoli, Alice A Tomei, Cherie L Stabler
To explore the effects immune-isolating encapsulation has on the insulin secretion of pancreatic islets and to improve our ability to quantitatively describe the glucose-stimulated insulin release (GSIR) of pancreatic islets, we conducted dynamic perifusion experiments with isolated human islets. Free (unencapsulated) and hydrogel encapsulated islets were perifused, in parallel, using an automated multi-channel system that allows sample collection with high temporal resolution. Results indicated that free human islets secrete less insulin per unit mass or islet equivalent (IEQ) than murine islets and with a less pronounced first-phase peak...
September 2, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/28864913/pancreatic-neuro-insular-network-in-young-mice-revealed-by-3d-panoramic-histology
#19
Shiue-Cheng Tang, Chia-Ning Shen, Pei-Yu Lin, Shih-Jung Peng, Hung-Jen Chien, Ya-Hsien Chou, Chester E Chamberlain, Pankaj J Pasricha
AIMS/HYPOTHESIS: It has been proposed that the neuro-insular network enables rapid, synchronised insulin secretion. However, to date, acquiring the pancreatic tissue map to study the neural network remains a challenging task as there is a lack of feasible approaches for large-scale tissue analysis at the organ level. Here, we have developed 3-dimensional (3D) panoramic histology to characterise the pancreatic neuro-insular network in young mice. METHODS: Pancreases harvested from young wild-type B6 mice (3 and 8 weeks old) and db/db mice (3 weeks old; db/db vs db/+) were used to develop 3D panoramic histology...
September 1, 2017: Diabetologia
https://www.readbyqxmd.com/read/28864875/deciphering-the-pathogenesis-of-human-type-1-diabetes-t1d-by-interrogating-t-cells-from-the-scene-of-the-crime
#20
REVIEW
Sally C Kent, Stuart I Mannering, Aaron W Michels, Jenny Aurielle B Babon
PURPOSE OF REVIEW: Autoimmune-mediated destruction of insulin-producing β-cells within the pancreas results in type 1 diabetes (T1D), which is not yet preventable or curable. Previously, our understanding of the β-cell specific T cell repertoire was based on studies of autoreactive T cell responses in the peripheral blood of patients at risk for, or with, T1D; more recently, investigations have included immunohistochemical analysis of some T cell specificities in the pancreas from organ donors with T1D...
September 2, 2017: Current Diabetes Reports
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