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https://www.readbyqxmd.com/read/29145148/honokiol-protects-pancreatic-%C3%AE-cell-against-high-glucose-and-intermittent-hypoxia-induced-injury-by-activating-nrf2-are-pathway-in-vitro-and-in-vivo
#1
Chen-Guang Li, Chang-Lin Ni, Min Yang, Yun-Zhao Tang, Zhu Li, Yan-Juan Zhu, Zhen-Huan Jiang, Bei Sun, Chun-Jun Li
Obstructive sleep apnea hypopnea syndrome (OSAHS) is associated with glucose intolerance, insulin resistance and type 2 diabetes mellitus (T2DM). Although several studies have revealed that intermittent hypoxia (IH) in OSAHS may further aggravate pancreatic β cell damage and promote the evolution of type 2 diabetes (T2DM) by increasing oxidative stress, the underlying mechanisms are unclear. Honokiol, a potent radical scavenger, has been demonstrated to ameliorate oxidative stress in many cases. The present study aimed to explore the potential mechanism of IH and diabetes synergistically damage and destruct the pancreatic β cell, examine the effects of honokiol on ameliorating pancreatic β cell injury in this context and explore the mechanism of such effects...
November 13, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29138225/androgen-signaling-expands-%C3%AE-cell-mass-in-male-rats-and-%C3%AE-cell-androgen-receptor-is-degraded-under-high-glucose-conditions
#2
Naoki Harada, Yasuhiro Yoda, Yusuke Yotsumoto, Tatsuya Masuda, Yuji Takahashi, Takahiro Katsuki, Kenji Kai, Nobuaki Shiraki, Hiroshi Inui, Ryoichi Yamaji
A deficient pancreatic β-cell mass increases the risk of type 2 diabetes mellitus. Here, we investigated the effects of testosterone on the development of pancreatic β-cell mass in male rats. The β-cell mass of male rats castrated at 6 weeks of age was reduced to ~30% of that of control rats at 16 weeks of age, and castration caused glucose intolerance. Loss of β-cell mass occurred due to decreases in islet density/pancreas and β-cell cluster size. Castration was negatively associated with the number of Ki67-positive β-cells and positively associated with the number of TUNEL-positive β-cells...
November 14, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29128354/angiotensin-converting-enzyme-2-regulates-mitochondrial-function-in-pancreatic-%C3%AE-cells
#3
Ting-Ting Shi, Fang-Yuan Yang, Chang Liu, Xi Cao, Jing Lu, Xue-Lian Zhang, Ming-Xia Yuan, Chen Chen, Jin-Kui Yang
Mitochondrial metabolism plays an essential role in the regulation of insulin release and glucose homeostasis. Evidence demonstrated that the angiotensin-converting enzyme 2 (ACE2) participates in the regulation of glucose metabolism, however, its role in mitochondrial metabolism remains unclear. The purpose of our study was to determine if ACE2 can regulate mitochondrial function in pancreatic β-cells. We found that ACE2 over-expression restored glucose-stimulated insulin secretion (GSIS) and mitochondrial membrane potential (MMP) in the presence of H2O2 in INS-1 cells...
November 8, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29122960/mir-335-overexpression-impairs-insulin-secretion-through-defective-priming-of-insulin-vesicles
#4
Vishal A Salunkhe, Jones K Ofori, Nikhil R Gandasi, Sofia A Salö, Sofia Hansson, Markus E Andersson, Anna Wendt, Sebastian Barg, Jonathan L S Esguerra, Lena Eliasson
MicroRNAs contribute to the maintenance of optimal cellular functions by fine-tuning protein expression levels. In the pancreatic β-cells, imbalances in the exocytotic machinery components lead to impaired insulin secretion and type 2 diabetes (T2D). We hypothesize that dysregulated miRNA expression exacerbates β-cell dysfunction, and have earlier shown that islets from the diabetic GK-rat model have increased expression of miRNAs, including miR-335-5p (miR-335). Here, we aim to determine the specific role of miR-335 during development of T2D, and the influence of this miRNA on glucose-stimulated insulin secretion and Ca(2+)-dependent exocytosis...
November 2017: Physiological Reports
https://www.readbyqxmd.com/read/29119245/development-and-characterisation-of-a-novel-glucagon-like-peptide-1-receptor-antibody
#5
Emma K Biggs, Lihuan Liang, Jacqueline Naylor, Shimona Madalli, Rachel Collier, Matthew P Coghlan, David J Baker, David C Hornigold, Peter Ravn, Frank Reimann, Fiona M Gribble
AIMS/HYPOTHESIS: Glucagon like peptide-1 (GLP-1) enhances glucose-dependent insulin secretion by binding to GLP-1 receptors (GLP1Rs) on pancreatic beta cells. GLP-1 mimetics are used in the clinic for the treatment of type 2 diabetes, but despite their therapeutic success, several clinical effects of GLP-1 remain unexplained at a mechanistic level, particularly in extrapancreatic tissues. The aim of this study was to generate and characterise a monoclonal antagonistic antibody for the GLP1R for use in vivo...
November 9, 2017: Diabetologia
https://www.readbyqxmd.com/read/29111283/pancreatic-islet-autonomous-effect-of-arsenic-on-insulin-secretion-through-endoplasmic-reticulum-stress-autophagy-pathway
#6
Wei Wu, Xiaofeng Yao, Liping Jiang, Qiaoting Zhang, Jie Bai, Tianming Qiu, Lei Yang, Ni Gao, Guang Yang, Xiaofang Liu, Min Chen, Xiance Sun
Inorganic arsenic is a worldwide environmental pollutant. Arsenic's relationship with the incidence of diabetes arouses concerns on its etiological mechanism. In this study, the glucose-stimulated insulin secretion (GSIS) from isolated pancreatic islets of As2O3-treated mice was significantly lower than that of control mice. It indicated that the effect of As2O3-inhibited GSIS was pancreatic islet-autonomous. The level of phospho-PERK (p-PERK), a biomarker of endoplasmic reticulum (ER) stress, in pancreas of As2O3-treated mice was increased significantly...
October 27, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29101219/mir-204-controls-glucagon-like-peptide-1-receptor-expression-and-agonist-function
#7
SeongHo Jo, Junqin Chen, Guanlan Xu, Truman B Grayson, Lance A Thielen, Anath Shalev
Glucagon-like peptide 1 receptor (GLP1R) agonists are widely used to treat diabetes. However, their function is dependent on adequate GLP1R expression, which is downregulated in diabetes. GLP1R is highly expressed on pancreatic beta cells and activation by endogenous incretin or GLP1R agonists increases cAMP generation, which stimulates glucose-induced beta cell insulin secretion and helps maintain glucose homeostasis. We now have discovered that the highly beta cell-enriched microRNA, miR-204, directly targets the 3'UTR of GLP1R and thereby downregulates its expression in the beta-cell-derived rat INS-1 cell line and primary mouse and human islets...
November 3, 2017: Diabetes
https://www.readbyqxmd.com/read/29057810/synthesis-characterization-and-biological-evaluations-of-1-3-5-triazine-derivatives-of-metformin-cyclization-with-berberine-and-magnolol-in-the-presence-of-sodium-methylate
#8
Han Cao, Shili Liao, Wenjing Zhong, Xuerong Xiao, Jiancheng Zhu, Weimin Li, Xia Wu, Yifan Feng
The novel target products were synthesized in the formation of a triazine ring from berberine, magnolol, and metformin catalyzed by sodium methylate. The structures of products 1-3 were firstly confirmed by extensive spectroscopic analyses and single-crystal X-ray diffraction. The crystal structures of the target product 2 and the intermediate product 7b were reported for the first time. All target products were evaluated for their anti-inflammatory and antidiabetic activities against INS-1 and RAW264.1 cells in vitro and all products showed excellent anti-inflammatory effects and anti-insulin resistance effects...
October 18, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29042678/carnosine-scavenging-of-glucolipotoxic-free-radicals-enhances-insulin-secretion-and-glucose-uptake
#9
Michael J Cripps, Katie Hanna, Charlie Lavilla, Sophie R Sayers, Paul W Caton, Craig Sims, Luigi De Girolamo, Craig Sale, Mark D Turner
The worldwide prevalence of diabetes has risen to 8.5% among adults, which represents a staggering rise in prevalence from 4.7% in 1980. Whilst some treatments work by increasing insulin secretion, over time their effectiveness decreases. We aim to increase insulin secretion by developing strategies that work through mechanisms independent of current treatment options. Isolated CD1 mouse islets, INS-1 pancreatic β-cells, or C2C12 mouse myotubes were incubated in standard tissue culture media, or media supplemented with 28 mM glucose, 200 μM palmitic acid, and 200 μM oleic acid as a cellular model of diabetic glucolipotoxicity...
October 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29038359/hyperoxia-reduces-insulin-release-and-induces-mitochondrial-dysfunction-with-possible-implications-for-hyperoxic-treatment-of-neonates
#10
Ingrid Hals, Tsuyoshi Ohki, Rinku Singh, Zuheng Ma, Anneli Björklund, Chandima Balasuriya, Hanne Scholz, Valdemar Grill
We previously showed that hyperoxia in vitro negatively affects beta cells of the rat. Here, we tested for possible clinical significance as well as mitochondrial interactions by hyperoxia, using human islets (function and viability), INS-1 832/13 cells (mitochondrial metabolism), and mouse neonates (effects in vivo). Lastly, we assessed relevant parameters in a cohort of individuals born preterm and then exposed to hyperoxia. Human islets and INS-1 832/13 cells were exposed to 24 h of hyperoxia (90-92% oxygen)...
October 2017: Physiological Reports
https://www.readbyqxmd.com/read/29032333/glucagon-like-peptide-1-improves-%C3%AE-cell-dysfunction-by-suppressing-the-mir-27a-induced-downregulation-of-atp-binding-cassette-transporter-a1
#11
Yue Yao, Yi Xu, Wei Wang, Jinchao Zhang, Qiang Li
Lipotoxicity is considered one of the main causes of deterioration in β-cells function. Glucagon-like peptide-1 (GLP-1) has been revealed to protect and improve pancreatic β-cell function against lipotoxicity. However, the mechanism behind these is largely unknown. The aim of this study was to investigate the effects of GLP-1 on cholesterol-induced lipotoxicity in INS-1 cells and examine the underlying mechanisms. The cell viability was determined, and caspase-3 was used to assess the effects of GLP-1 on cholesterol-induced apoptosis...
October 12, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29018279/sodium-fluorocitrate-having-protective-effect-on-palmitate-induced-beta-cell-death-improves-hyperglycemia-in-diabetic-db-db-mice
#12
Ik-Rak Jung, Sung-E Choi, Seung A Hong, Yoonjung Hwang, Yup Kang
Beta cell loss and insulin resistance play roles in the pathogenesis of type 2 diabetes. Elevated levels of free fatty acids in plasma might contribute to the loss of beta cells. The objective of this study was to find a chemical that could protect against palmitate-induced beta cell death and investigate whether such chemical could improve hyperglycemia in mouse model of type 2 diabetes. Sodium fluorocitrate (SFC), an aconitase inhibitor, was found to be strongly and specifically protective against palmitate-induced INS-1 beta cell death...
October 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28988953/meddling-with-fate-the-proteasomal-deubiquitinating-enzymes
#13
REVIEW
Stefanie A H de Poot, Geng Tian, Daniel Finley
Three deubiquitinating enzymes-Rpn11, Usp14, and Uch37-are associated with the proteasome regulatory particle. These enzymes allow proteasomes to remove ubiquitin from substrates before they are translocated into the core particle to be degraded. Although the translocation channel is too narrow for folded proteins, the force of translocation unfolds them mechanically. As translocation proceeds, ubiquitin chains bound to substrate are drawn to the channel's entry port, where they can impede further translocation...
November 10, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28968609/inhibition-of-prenylation-promotes-caspase-3-activation-lamin-b-degradation-and-loss-in-metabolic-cell-viability-in-pancreatic-%C3%AE-cells
#14
Khadija G Syeda, Anjan Kowluru
BACKGROUND/AIMS: Lamins are intermediate filament proteins that constitute the main components of the lamina underlying the inner-nuclear membrane and serve to organize chromatin. Lamins (e.g., lamin B) undergo posttranslational modifications (e.g., isoprenylation) at their C-terminal cysteine residues. Such modifications are thought to render optimal association of lamins with the nuclear envelop. Using human islets, rodent islets, and INS-1 832/13 cells, we recently reported significant metabolic defects under glucotoxic and endoplasmic reticulum (ER) stress conditions, including caspase 3 activation and lamin B degradation...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28956099/arsenite-and-methylarsonite-inhibit-mitochondrial-metabolism-and-glucose-stimulated-insulin-secretion-in-ins-1-832-13-%C3%AE-cells
#15
E N Dover, R Beck, M C Huang, C Douillet, Z Wang, E L Klett, Miroslav Stýblo
Growing evidence suggests that exposure to environmental contaminants contributes to the current diabetes epidemic. Inorganic arsenic (iAs), a drinking water and food contaminant, is one of the most widespread environmental diabetogens according to epidemiological studies. Several schemes have been proposed to explain the diabetogenic effects of iAs exposure; however, the exact mechanism remains unknown. We have shown that in vitro exposure to low concentrations of arsenite (iAs(III)) or its trivalent methylated metabolites, methylarsonite (MAs(III)) and dimethylarsinite (DMAs(III)), inhibits glucose-stimulated insulin secretion (GSIS) from isolated pancreatic islets, with little effect on insulin transcription or total insulin content...
September 27, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28955641/nanoformulation-of-leonotis-leonurus-to-improve-its-bioavailability-as-a-potential-antidiabetic-drug
#16
Frank Odei-Addo, Ranjita Shegokar, Rainer H Müller, R-A Levendal, Carminita Frost
Nanostructured lipid carriers (NLCs) of Leonotis leonurus were successfully produced using high-pressure homogenisation (HPH) on a LAB 40 homogeniser. The particle size was determined for the formulation as well as short-term stability study. The formulation was exposed to Chang liver cells for a glucose uptake study and to INS-1 cells for a chronic insulin release study under normoglycaemic and hyperglycaemic conditions. The particle size of the extract NLC was 220 nm with a PdI of 0.08 after homogenisation at 800 bar...
October 2017: 3 Biotech
https://www.readbyqxmd.com/read/28928397/atorvastatin-but-not-pravastatin-impairs-mitochondrial-function-in-human-pancreatic-islets-and-rat-%C3%AE-cells-direct-effect-of-oxidative-stress
#17
Francesca Urbano, Marco Bugliani, Agnese Filippello, Alessandra Scamporrino, Stefania Di Mauro, Antonino Di Pino, Roberto Scicali, Davide Noto, Agata Maria Rabuazzo, Maurizio Averna, Piero Marchetti, Francesco Purrello, Salvatore Piro
Statins are a class of drugs widely prescribed as frontline therapy for lowering plasma LDL-cholesterol in cardiovascular risk prevention. Several clinical reports have recently suggested an increased risk of type 2 diabetes associated with chronic use of these drugs. The pathophysiology of this effect remains to be fully elucidated but impaired β-cell function constitutes a potential mechanism. The aim of this study was to explore the effect of a chronic treatment with lipophilic and hydrophilic statins on β-cell function, using human pancreatic islets and rat insulin-secreting INS-1 cells; we particularly focused on the role of mitochondria and oxidative stress...
September 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28900515/fluorocarbons-enhance-intracellular-delivery-of-short-stat3-sensors-and-enable-specific-imaging
#18
Valeriy Metelev, Surong Zhang, Shaokuan Zheng, Anand T N Kumar, Alexei Bogdanov
Short oligonucleotide sequences are now being widely investigated for their potential therapeutic properties. The modification of oligonucleotide termini with short fluorinated residues is capable of drastically altering their behavior in complex in vitro and in vivo systems, and thus may serve to greatly enhance their therapeutic potential. The main goals of our work were to explore: 1) how modification of STAT3 transcription factor-binding oligodeoxynucleotide (ODN) duplexes (ODND) with one or two short fluorocarbon (FC)-based residues would change their properties in vitro and in vivo, and if so, how this would affect their intracellular uptake by cancer cells, and 2) the ability of such modified ODND to form non-covalent complexes with FC-modified carrier macromolecule...
2017: Theranostics
https://www.readbyqxmd.com/read/28893685/protective-effects-of-a-g-lucidum-proteoglycan-on-ins-1-cells-against-iapp-induced-apoptosis-via-attenuating-endoplasmic-reticulum-stress-and-modulating-chop-jnk-pathways
#19
Yan-Ming He, Qiang Zhang, Min Zheng, Zhao-Hua Fan, Yun-Hao Li, Dan Zhang, Zeng Zhang, Sha-Sha Yuan, Yan-Yan Wang, Ping Zhou, Hong-Jie Yang
Fudan-Yueyang-G. lucidum (FYGL) is a water-soluble macromolecular proteoglycan extracted from Ganoderma lucidum which has been used for health promotion for a long time in China. The aim of this study was to investigate the protective effects of FYGL on INS-1 rat insulinoma beta cells against IAPP-induced cell apoptosis, as well as the underlying mechanisms. The results showed that apoptotic cells were significantly increased when incubated with islet amyloid polypeptide (IAPP). However, cytotoxicity of IAPP was significantly attenuated by co-incubation of the cells with FYGL...
September 8, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28882892/structural-features-of-human-inositol-phosphate-multikinase-rationalize-its-inositol-phosphate-kinase-and-phosphoinositide-3-kinase-activities
#20
Huanchen Wang, Stephen B Shears
Human inositol phosphate multikinase (HsIPMK) critically contributes to intracellular signaling through its inositol-1,4,5-trisphosphate (Ins(1,4,5)P3) 3-kinase and phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) 3-kinase activities. This catalytic profile is not conserved; orthologs from Arabidopsis thaliana and Saccharomyces cerevisiae are predominantly Ins(1,4,5)P3 6-kinases, and the plant enzyme cannot phosphorylate PtdIns(4,5)P2 Therefore, crystallographic analysis of the yeast and plant enzymes, without bound inositol phosphates, do not structurally rationalize HsIPMK activities...
November 3, 2017: Journal of Biological Chemistry
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