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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
#1
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
#2
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
#3
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
#4
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...
September 7, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28869857/bde-47-and-bde-85-stimulate-insulin-secretion-in-ins-1-832-13-pancreatic-%C3%AE-cells-through-the-thyroid-receptor-and-akt
#5
Shpetim Karandrea, Huquan Yin, Xiaomei Liang, Emma A Heart
PBDEs (polybrominated diphenyl ethers) are environmental pollutants that have been linked to the development of type 2 diabetes, however, the precise mechanisms are not clear. Particularly, their direct effect on insulin secretion is unknown. In this study, we show that two PBDE congeners, BDE-47 and BDE-85, potentiate glucose-stimulated insulin secretion (GSIS) in INS-1 832/13 cells. This effect of BDE-47 and BDE-85 on GSIS was dependent on thyroid receptor (TR). Both BDE-47 and BDE-85 (10μM) activated Akt during an acute exposure...
September 1, 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/28866834/insulin-and-osteocalcin-further-evidence-for-a-mutual-cross-talk
#6
Francesco L Bilotta, Biagio Arcidiacono, Sebastiano Messineo, Marta Greco, Eusebio Chiefari, Domenico Britti, Tomoko Nakanishi, Daniela P Foti, Antonio Brunetti
PURPOSE: In the last few years, bone has been recognized as an endocrine organ that modulates glucose metabolism by secretion of osteocalcin, an osteoblast-specific hormone, that influences fat deposition and blood sugar levels. To date, however, very few in vitro models have been developed to investigate, at the molecular levels, the relationship between glucose, insulin and osteocalcin. This study aims at covering this gap. METHODS: We studied osteogenic differentiation, osteocalcin gene expression, and osteblast-mediated insulin secretion, using cultured MG-63 human osteoblast-like cells that underwent glucotoxicity and insulin resistance...
September 2, 2017: Endocrine
https://www.readbyqxmd.com/read/28863367/monomeric-cocoa-catechins-enhance-%C3%AE-cell-function-by-increasing-mitochondrial-respiration
#7
Thomas J Rowley, Benjamin F Bitner, Jason D Ray, Daniel R Lathen, Andrew T Smithson, Blake W Dallon, Chase J Plowman, Benjamin T Bikman, Jason M Hansen, Melanie R Dorenkott, Katheryn M Goodrich, Liyun Ye, Sean F O'Keefe, Andrew P Neilson, Jeffery S Tessem
A hallmark of type 2 diabetes (T2D) is β-cell dysfunction and the eventual loss of functional β-cell mass. Therefore, mechanisms that improve or preserve β-cell function could be used to improve the quality of life of individuals with T2D. Studies have shown that monomeric, oligomeric and polymeric cocoa flavanols have different effects on obesity, insulin resistance and glucose tolerance. We hypothesized that these cocoa flavanols may have beneficial effects on β-cell function. INS-1 832/13-derived β-cells and primary rat islets cultured with a monomeric catechin-rich cocoa flavanol fraction demonstrated enhanced glucose-stimulated insulin secretion, while cells cultured with total cocoa extract and with oligomeric or polymeric procyanidin-rich fraction demonstrated no improvement...
July 27, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28842702/stigmasterol-prevents-glucolipotoxicity-induced-defects-in-glucose-stimulated-insulin-secretion
#8
Meliza G Ward, Ge Li, Valéria C Barbosa-Lorenzi, Mingming Hao
Type 2 diabetes results from defects in both insulin sensitivity and insulin secretion. Elevated cholesterol content within pancreatic β-cells has been shown to reduce β-cell function and increase β-cell apoptosis. Hyperglycemia and dyslipidemia contribute to glucolipotoxicity that leads to type 2 diabetes. Here we examined the capacity of glucolipotoxicity to induce free cholesterol accumulation in human pancreatic islets and the INS-1 insulinoma cell line. Glucolipotoxicity treatment increased free cholesterol in β-cells, which was accompanied by increased reactive oxygen species (ROS) production and decreased insulin secretion...
August 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28833446/necrotic-cell-death-occur-via-jnk-pathway-with-the-activity-of-transcription-factor-c-jun-by-4-mc-in-ins-1-cell-line
#9
Ayse Karatug Kacar, Sehnaz Bolkent
In this study, it was aimed to determine the doses of 4-methylcatechol causing cell death in rat insulinoma β-cells (INS-1), to find out the type of cellular death at these doses, and to investigate the molecular mechanism of cellular death occurring. More necrotic cells were observed than apoptosis with the administration of 350, 400, and 450 μM 4-methylcatechol. Lactate dehydrogenase levels, reactive oxygen species, mitochondrial potential loss, ATP and GTP losses increased at these doses. The JNK and ERK cellular pathway were screened...
August 21, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28828705/glucotoxicity-promotes-aberrant-activation-and-mislocalization-of-ras-related-c3-botulinum-toxin-substrate-1-rac1-and-metabolic-dysfunction-in-pancreatic-islet-%C3%AE-cells-reversal-of-such-metabolic-defects-by-metformin
#10
Sartaj Baidwan, Anil Chekuri, DiAnna L Hynds, Anjaneyulu Kowluru
Emerging evidence suggests that long-term exposure of insulin-secreting pancreatic β-cells to hyperglycemic (HG; glucotoxic) conditions promotes oxidative stress, which, in turn, leads to stress kinase activation, mitochondrial dysfunction, loss of nuclear structure and integrity and cell apoptosis. Original observations from our laboratory have proposed that Rac1 plays a key regulatory role in the generation of oxidative stress and downstream signaling events culminating in the onset of dysfunction of pancreatic β-cells under the duress of metabolic stress...
August 21, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28828521/recombinant-lactococcus-lactis-expressing-bioactive-exendin-4-to-promote-insulin-secretion-and-beta-cell-proliferation-in-vitro
#11
Zhu Zeng, Rui Yu, Fanglei Zuo, Bo Zhang, Huiqin Ma, Shangwu Chen
In recent years, therapeutic peptides have garnered great interest in the pharmaceutical industry for the treatment of diabetes. Lactic acid bacteria (LAB) are an appealing vehicle for safe and convenient oral delivery of bioactive peptide and protein drugs. Exendin-4 (Exd4) is a glucagon-like protein-1 (GLP-1) receptor agonist that is considered an excellent therapeutic peptide drug for type 2 diabetes due to its longer-lasting bioactivity, resulting from resistance to dipeptidyl peptidase 4. We explored Lactococcus lactis with the nisin-controlled gene expression (NICE) system as an oral delivery system for recombinant (r) Exd4 peptide in situ...
August 21, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28817206/loureirin-b-promotes-insulin-secretion-through-inhibition-of-katp-channel-and-influx-of-intracellular-calcium
#12
Yijie Sha, Yuelin Zhang, Jing Cao, Kai Qian, Bing Niu, Qin Chen
The development of new diabetes drugs continues to be explored. Loureirin B, a flavonoid, extracted from Dracaena cochinchinensis, has been confirmed to increase insulin secretion and decrease blood glucose levels. For searching the promotion of insulin secretion with the treatment of loureirin B, experiments were employed based on cell experiments and computational methods. Firstly, promotion of insulin secretion was dependent on extracellular glucose concentration. At the genetic level, loureirin B enhanced the relative mRNA level of Pdx-1 and MafA...
August 17, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28800882/salvianolic-acid-b-inhibits-intermittent-high-glucose-induced-ins-1-cell-apoptosis-through-regulation-of-bcl-2-proteins-and-mitochondrial-membrane-potential
#13
Shanjun Tao, Younan Ren, Haowen Zheng, Mengqiu Zhao, Xu Zhang, Yuanmei Zhu, Jieren Yang, Shuguo Zheng
Blood glucose fluctuations, also referred to as intermittent high glucose, have been validated to be more harmful than sustained high glucose in exacerbating pancreatic dysfunction by inducing β cell apoptosis. Salvianolic acid B (Sal B), an aqueous component of Salvia miltiorrhiza, has been proved beneficial to pancreatic islet function in diabetes, but the underlying mechanisms remain to be elucidated. The present study investigated the protective effect of Sal B on INS-1 cells exposed to intermittent high glucose and the possible mechanisms implicated...
August 8, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28798936/antidiabetic-micro-nanoaggregates-from-ge-gen-qin-lian-tang-decoction-increase-absorption-of-baicalin-and-cellular-antioxidant-activity-in-vitro
#14
Dai Lin, Qian Du, Huiqin Wang, Guanzhen Gao, Jianwu Zhou, Lijing Ke, Tianbao Chen, Chris Shaw, Pingfan Rao
The antidiabetic effects of Ge-Gen-Qin-Lian-Tang decoction (GQD) have been proven clinically. In a pharmacological study conducted on STZ-induced diabetic rats, the constitutive aggregates/sediments of Ge-Gen-Qin-Lian-Tang decoction exhibited stronger hypoglycemic and antioxidant activities compared to the soluble compositions. This study aims to demonstrate the pharmacological properties of aggregates derived from GQD by measuring permeability of the active monomer phytochemicals (e.g., baicalin) in a Caco-2 cell monolayer and determine the cellular viability, intracellular redox status (MDA and SOD), and insulin secretion of pancreatic β-cell line, INS-1, following STZ-induced oxidative stress...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28797815/structure-of-a-pectic-polysaccharide-from-pseudostellaria-heterophylla-and-stimulating-insulin-secretion-of-ins-1-cell-and-distributing-in-rats-by-oral
#15
Jinlong Chen, Wensheng Pang, Yongjun Kan, Li Zhao, Zhaodong He, Wentao Shi, Bin Yan, Hong Chen, Juan Hu
A water-soluble, pectic polysaccharide named as 0.5MSC-F isolated from Pseudostellaria Heterophylla with a molecular weight of 4.8×10(4) Da that was composed of rhamnose, galactose, arabinose, and galacturonic acid which the major monosaccharide contents range up to 63.20%. Where the main chain was consists of 1,4-linked galacturonic acid and a small amount of 1,2-linked rhamnose was embedded into backbone to connect alternative galacturonic acid in the form of Rhamnogalacturonan I (RG-I) structure. 1, 5-linked arabinose through C-4 of 1, 2-linked rhamnose, another 1, 3 or 1,6-linked galactose through C-4 of 1, 2-linked rhamnose, was interconnected to branch chain...
August 7, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28793264/vesicle-docking-is-a-key-target-of-local-pi-4-5-p2-metabolism-in-the-secretory-pathway-of-ins-1-cells
#16
Chen Ji, Fan Fan, Xuelin Lou
Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) signaling is transient and spatially confined in live cells. How this pattern of signaling regulates transmitter release and hormone secretion has not been addressed. We devised an optogenetic approach to control PI(4,5)P2 levels in time and space in insulin-secreting cells. Combining this approach with total internal reflection fluorescence microscopy, we examined individual vesicle-trafficking steps. Unlike long-term PI(4,5)P2 perturbations, rapid and cell-wide PI(4,5)P2 reduction in the plasma membrane (PM) strongly inhibits secretion and intracellular Ca(2+) concentration ([Ca(2+)]i) responses, but not sytaxin1a clustering...
August 8, 2017: Cell Reports
https://www.readbyqxmd.com/read/28768836/s-equol-activates-camp-signaling-at-the-plasma-membrane-of-ins-1-pancreatic-%C3%AE-cells-and-protects-against-streptozotocin-induced-hyperglycemia-by-increasing-%C3%AE-cell-function-in-male-mice
#17
Hiroko Horiuchi, Atsuko Usami, Rie Shirai, Naoki Harada, Shinichi Ikushiro, Toshiyuki Sakaki, Yoshihisa Nakano, Hiroshi Inui, Ryoichi Yamaji
Background:S-equol, which is enantioselectively produced from daidzein by gut microbiota, has been suggested as a chemopreventive agent against type 2 diabetes mellitus (T2DM), but the underlying mechanisms remain unclear.Objective: We investigated the effects of S-equol on pancreatic β-cell function.Methods: β-Cell growth and insulin secretion were evaluated with male Institute of Cancer Research mice and isolated pancreatic islets from the mice, respectively. The mechanisms by which S-equol stimulated β-cell response were examined in INS-1 β-cells...
September 2017: Journal of Nutrition
https://www.readbyqxmd.com/read/28754588/substance-p-preserves-pancreatic-%C3%AE-cells-in-streptozotocin-induced-type-1-diabetic-mice
#18
Nunggum Jung, Jihyun Um, Do Yeon Kim, Maria Jose Dubon, Yeji Byeon, Dongjin Kim, Youngsook Son, Ki-Sook Park
Preservation of the pancreatic β-cell population is required for the development of therapies for diabetes, which is caused by a decrease in β-cells. Here, we demonstrate the antidiabetic effects of substance P (SP) in type 1 diabetes (T1D) mice induced with streptozotocin. SP enhanced the compensatory proliferation of β-cells in order to restore β-cells in response to acute injury induced by a single high-dose of streptozotocin. However, SP affected neither the basal proliferation of β-cells nor their apoptosis...
July 25, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28744320/quantification-of-tumor-vascular-permeability-and-blood-volume-by-positron-emission-tomography
#19
Haojun Chen, Xiao Tong, Lixin Lang, Orit Jacobson, Bryant C Yung, Xiangyu Yang, Ruiliang Bai, Dale O Kiesewetter, Ying Ma, Hua Wu, Gang Niu, Xiaoyuan Chen
Purpose: Evans Blue (EB) is an azo dye that binds quantitatively with serum albumin. With an albumin binding, NOTA conjugated truncated Evan's blue (NEB) dye derived PET tracer, we aimed to establish a strategy for evaluating vascular permeability in malignant tumors via non-invasive PET. Experimental design: Sixty-minute dynamic PET using [(18)F]FAl-NEB was performed in three xenograft tumor models including INS-1 rat insulinoma, UM-SCC-22B human head and neck carcinoma and U-87 MG human glioblastoma. Tumor vascular permeability was quantified by the difference of the slopes between tumor and blood time-activity curve (TACs, expressed as Ps )...
2017: Theranostics
https://www.readbyqxmd.com/read/28731171/protective-role-of-pollen-typhae-total-flavone-against-the-palmitic-acid-induced-impairment-of-glucose-stimulated-insulin-secretion-involving-gpr40-signaling-in-ins-1-cells
#20
Xiao-Tao Feng, Hui-Ming Duan, Shuang-Lei Li
Prolonged elevated levels of free fatty acids (FFAs) contribute to the impairment of insulin secretion function of pancreatic β cells, a hallmark of type 2 diabetes, which is partly attributed to the dysfunction of G-protein-coupled receptor 40 (GPR40) signaling. Pollen Typhae total flavone (PTF), an extract from a Chinese herbal medicine named Pollen Typhae, has been reported to effectively treat type 2 diabetes, but the underlying mechanisms remain to be fully elucidated. In the present study, palmitic acid (PA), a saturated fatty acid, severely impaired glucose-stimulated insulin secretion (GSIS) in a time-dependent manner in INS-1 cells, and PTF treatment prevented the impairment in a dose-dependent manner...
July 18, 2017: International Journal of Molecular Medicine
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