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https://www.readbyqxmd.com/read/27914526/jiawei-erzhiwan-improves-menopausal-metabolic-syndrome-by-enhancing-insulin-secretion-in-pancreatic-%C3%AE-cells
#1
Xiao-Meng Wan, Mu Zhang, Pei Zhang, Zhi-Shen Xie, Feng-Guo Xu, Ping Zhou, Shi-Ping Ma, Xiao-Jun Xu
Menopausal metabolic syndrome (MMS) is a series of syndrome caused by ovarian function decline and hormone insufficiency, and is a high risk factor for cardiovascular diseases (CVD) and type II diabetes mellitus (T2DM). Erzhiwan (EZW), composed of Herba Ecliptae and Fructus Ligustri Lucidi, is a traditional Chinese herbal formula that has been used to treat menopausal syndrome for many years. We added Herba Epimedii, Radix Rehmanniae, and Fructus Corni into EZW, to prepare a new formula, termed Jiawei Erzhiwan (JE)...
November 2016: Chinese Journal of Natural Medicines
https://www.readbyqxmd.com/read/27912197/rac1-nadph-oxidase-signaling-promotes-cd36-activation-under-glucotoxic-conditions-in-pancreatic-beta-cells
#2
Suma Elumalai, Udayakumar Karunakaran, In Kyu Lee, Jun Sung Moon, Kyu Chang Won
We recently reported that cluster determinant 36 (CD36), a fatty acid transporter, plays a pivotal role in glucotoxicity-induced β-cell dysfunction. However, little is known about how glucotoxicity influences CD36 expression. Emerging evidence suggests that the small GTPase Rac1 is involved in the pathogenesis of beta cell dysfunction in type 2 diabetes (T2D). The primary objective of the current study was to determine the role of Rac1 in CD36 activation and its impact on β-cell dysfunction in diabetes mellitus...
November 23, 2016: Redox Biology
https://www.readbyqxmd.com/read/27900263/islet-chrebp-%C3%AE-is-increased-in-diabetes-and-controls-chrebp-%C3%AE-and-glucose-induced-gene-expression-via-a-negative-feedback-loop
#3
Gu Jing, Junqin Chen, Guanlan Xu, Anath Shalev
OBJECTIVE: Carbohydrate-response element-binding protein (ChREBP) is the major transcription factor conferring glucose-induced gene expression in pancreatic islets, liver and adipose tissue. Recently, a novel ChREBP isoform, ChREBP-β, was identified in adipose tissue and found to be also expressed in islets and involved in glucose-induced beta cell proliferation. However, the physiological function of this less abundant β-isoform in the islet, and in diabetes, is largely unknown. The aims of the present study, therefore, were to determine how diabetes affects ChREBP-β and elucidate its physiological role in pancreatic beta cells...
December 2016: Molecular Metabolism
https://www.readbyqxmd.com/read/27865837/autophagy-protects-against-cholesterol-induced-apoptosis-in-pancreatic-%C3%AE-cells
#4
Jiahua Wu, Feijuan Kong, Qianqian Pan, Ying Du, Jun Ye, Fenping Zheng, Hong Li, Jiaqiang Zhou
Autophagy is believed to play an important role in maintaining homeostasis in pancreatic β-cells during insulin resistance. This study investigated the role of autophagy in β-cell damage induced by cholesterol and its possible activation mechanism. Rat and mouse pancreatic β-cell lines INS-1 and βTC-6 were incubated with cholesterol alone or in combination with autophagy inhibitors E-64d/Pepstatin A or bafilomycin A1. DAPI staining, western blotting, transmission electron microscopy and immunofluorescence were conducted to assess the effects of autophagy inhibitors on cholesterol-induced apoptosis and autophagy activity...
November 16, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27860445/an-in-situ-glucose-stimulated-insulin-secretion-assay-under-perfusion-bioreactor-conditions
#5
Jamie Sharp, Patrick Vermette
Perfusion bioreactors, unlike traditional in vitro cell culture systems, offer stringent control of physiological parameters such as pH, flow, temperature, and dissolved oxygen concentration which have been shown to have an impact on cellular behaviour and viability. Due to the relative infancy and the growing interest in these in vitro culture systems, detection methods to monitor cell function under dynamic perfusion bioreactor conditions remains one of the main challenges. In this study, INS-1 cells, a cell line which exhibit glucose-stimulated insulin secretion, were encapsulated in fibrin and cultured under perfusion bioreactor conditions for 48h and then exposed to either a high-, or low-glucose concentration for 24h...
November 14, 2016: Biotechnology Progress
https://www.readbyqxmd.com/read/27833848/neutral-ceramidase-enriched-exosomes-prevent-palmitic-acid-induced-insulin-resistance-in-h4iiec3-hepatocytes
#6
Qun Zhu, Rongping Zhu, Junfei Jin
Oversupply of free fatty acids such as palmitic acid (PA) from the portal vein may cause liver insulin resistance. Production of reactive oxygen species plays a pivotal role in PA-induced insulin resistance in H4IIEC3 hepatocytes. Recently, we found that exosomes secreted from INS-1 cells that were transfected with neutral ceramidase (NCDase) plasmids had raised NCDase activity; these NCDase-enriched exosomes could inhibit PA-induced INS-1 cell apoptosis. Here, we showed that PA reduced insulin-stimulated tyrosine phosphorylation of insulin receptor substrate 2 and decreased insulin-stimulated uptake of the fluorescent glucose analog 2-NBDG, confirming that insulin resistance occurred in PA-treated H4IIEC3 cells...
November 2016: FEBS Open Bio
https://www.readbyqxmd.com/read/27826714/exendin-4-promotes-pancreatic-%C3%AE-cell-proliferation-via-inhibiting-the-expression-of-wnt5a
#7
Xinger Wu, Weiwei Liang, Hongyu Guan, Juan Liu, Liehua Liu, Hai Li, Xiaoying He, Jing Zheng, Jie Chen, Xiaopei Cao, Yanbing Li
Exendin-4, a glucagon-like peptide-1 receptor agonist, is currently regarded as an effective therapeutic strategy for type-2 diabetes. Previous studies indicated that exendin-4 promoted β cell proliferation. However, the underlying mechanisms remain largely unknown. Recently it was reported that exendin-4 promoted pancreatic β cell proliferation by regulating the expression level of Wnt4. The present study was designed to investigate whether other Wnt isoforms take part in accommodation of β-cell proliferation...
November 9, 2016: Endocrine
https://www.readbyqxmd.com/read/27804997/a-presenilin-notch1-pathway-regulated-by-mir-375-mir-30a-and-mir-34a-mediates-glucotoxicity-induced-pancreatic-beta-cell-apoptosis
#8
Yating Li, Tao Zhang, Yuncai Zhou, Yi Sun, Yue Cao, Xiaoai Chang, Yunxia Zhu, Xiao Han
The presenilin-mediated Notch1 cleavage pathway plays a critical role in controlling pancreatic beta cell fate and survival. The aim of the present study was to investigate the role of Notch1 activation in glucotoxicity-induced beta cell impairment and the contributions of miR-375, miR-30a, and miR-34a to this pathway. We found that the protein levels of presenilins (PSEN1 and PSEN2), and NOTCH1 were decreased in INS-1 cells after treatment with increased concentrations of glucose, whereas no significant alteration of mRNA level of Notch1 was observed...
November 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27802439/metabolic-stress-induces-caspase-3-mediated-degradation-and-inactivation-of-farnesyl-and-geranylgeranyl-transferase-activities-in-pancreatic-%C3%AE-cells
#9
Rajakrishnan Veluthakal, Daleep K Arora, Marc L Goalstone, Renu A Kowluru, Anjaneyulu Kowluru
BACKGROUND/AIMS: At least 300 prenylated proteins are identified in the human genome; the majority of which partake in a variety of cellular processes including growth, differentiation, cytoskeletal organization/dynamics and vesicle trafficking. Aberrant prenylation of proteins is implicated in human pathologies including cancer; neurodegenerative diseases, retinitis pigmentosa, and premature ageing syndromes. Original observations from our laboratory have demonstrated that prenylation of proteins [small G-proteins and γ-subunits of trimeric G-proteins] is requisite for physiological insulin secretion...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27796421/hdac7-is-overexpressed-in-human-diabetic-islets-and-impairs-insulin-secretion-in-rat-islets-and-clonal-beta-cells
#10
Mahboubeh Daneshpajooh, Karl Bacos, Madhusudhan Bysani, Annika Bagge, Emilia Ottosson Laakso, Petter Vikman, Lena Eliasson, Hindrik Mulder, Charlotte Ling
AIMS/HYPOTHESIS: Pancreatic beta cell dysfunction is a prerequisite for the development of type 2 diabetes. Histone deacetylases (HDACs) may affect pancreatic endocrine function and glucose homeostasis through alterations in gene regulation. Our aim was to investigate the role of HDAC7 in human and rat pancreatic islets and clonal INS-1 beta cells (INS-1 832/13). METHODS: To explore the role of HDAC7 in pancreatic islets and clonal beta cells, we used RNA sequencing, mitochondrial functional analyses, microarray techniques, and HDAC inhibitors MC1568 and trichostatin A...
January 2017: Diabetologia
https://www.readbyqxmd.com/read/27764251/heterologous-expression-and-delivery-of-biologically-active-exendin-4-by-lactobacillus-paracasei-l14
#11
Zhu Zeng, Rui Yu, Fanglei Zuo, Bo Zhang, Deju Peng, Huiqin Ma, Shangwu Chen
Exendin-4, a glucagon-like protein-1 (GLP-1) receptor agonist, is an excellent therapeutic peptide drug for type 2 diabetes due to longer lasting biological activity compared to GLP-1. This study explored the feasibility of using probiotic Lactobacillus paracasei as an oral vector for recombinant exendin-4 peptide delivery, an alternative to costly chemical synthesis and inconvenient administration by injection. L. paracasei transformed with a plasmid encoding the exendin-4 gene (L. paracasei L14/pMG76e-exendin-4) with a constitutive promotor was successfully constructed and showed efficient secretion of exendin-4...
2016: PloS One
https://www.readbyqxmd.com/read/27763807/culture-at-low-glucose-up-regulates-mitochondrial-function-in-pancreatic-beta-cells-with-accompanying-effects-on-viability
#12
Ingrid K Hals, Rinku Singh, Zuheng Ma, Hanne Scholz, Anneli Björklund, Valdemar Grill
We tested whether exposure of beta cells at reduced glucose leads to mitochondrial adaptions and whether such adaptions modulate effects of hypoxia. Rat islets, human islets and INS-1 832/13 cells were pre-cultured short term at half standard glucose concentrations (5.5 mM for rat islets and cells, 2.75 mM for human islets) without overtly negative effects on subsequently measured function (insulin secretion and cellular insulin contents) or on viability. Culture at half standard glucose upregulated complex I and tended to upregulate complex II in islets and INS-1 cells alike...
October 20, 2016: Islets
https://www.readbyqxmd.com/read/27759122/formation-of-lamellar-micelle-like-oligomers-and-membrane-disruption-revealed-by-the-study-of-short-peptide-hiapp18-27
#13
Ying Wei, Jun Lu, Tong Lu, Feihong Meng, Jia Xu, Li Wang, Yang Li, Liping Wang, Fei Li
Prefibrillar amyloid aggregates of proteins are known as cytotoxic species and a common pathogenic factor for many degenerative diseases. The mechanism underlying the formation and cytotoxicity of prefibrillar aggregates is believed to be independent of the actual nature of the amyloid protein. In this study, we monitored the formation of the peptide oligomers and examined the disruptive effects of the oligomers on liposomes using the human islet amyloid polypeptide fragment hIAPP18-27 as a model peptide. We observed various morphologies of oligomers formed at different aggregation stages that precede the formation of mature amyloid fibrils...
October 19, 2016: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/27729786/sustained-release-of-hepatocyte-growth-factor-by-cationic-self-assembling-peptide-heparin-hybrid-hydrogel-improves-%C3%AE-cell-survival-and-function-through-modulating-inflammatory-response
#14
Shuyun Liu, Lanlan Zhang, Jingqiu Cheng, Yanrong Lu, Jingping Liu
Inflammatory response is a major cause of grafts dysfunction in islet transplantation. Hepatocyte growth factor (HGF) had shown anti-inflammatory activity in multiple diseases. In this study, we aim to deliver HGF by self-assembling peptide/heparin (SAP/Hep) hybrid gel to protect β-cell from inflammatory injury. The morphological and slow release properties of SAPs were analyzed. Rat INS-1 β-cell line was treated with tumor necrosis factor α in vitro and transplanted into rat kidney capsule in vivo, and the viability, apoptosis, function, and inflammation of β-cells were evaluated...
2016: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/27729543/real-time-imaging-of-intracellular-hydrogen-peroxide-in-pancreatic-islets
#15
Adam Neal, Austin Rountree, Kelly Kernan, Brian Van Yserloo, Huiliang Zhang, Benjamin J Reed, William Osborne, Wang Wang, Ian R Sweet
A real time method to measure intracellular H2O2 would be very impactful in characterizing rapid changes that occur in physiologic and pathophysiologic states. Current methods do not provide the sensitivity, specificity and spatiotemporal resolution needed for such experiments on intact cells. We developed the use of HyPer, a genetic indicator for H2O2 that can be expressed in the cytosol (cyto-HyPer) or the mitochondria (mito-HyPer) of live cells. INS-1 cells or islets were permeabilized and the cytosolic HyPer signal was a linear function of extracellular H2O2, allowing fluorescent cyto-HyPer signals to be converted to H2O2 concentrations...
October 11, 2016: Biochemical Journal
https://www.readbyqxmd.com/read/27699280/ptb-and-tiar-binding-to-insulin-mrna-3-and-5-utrs-implications-for-insulin-biosynthesis-and-messenger-stability
#16
Rikard G Fred, Syrina Mehrabi, Christopher M Adams, Nils Welsh
OBJECTIVES: Insulin expression is highly controlled on the posttranscriptional level. The RNA binding proteins (RBPs) responsible for this result are still largely unknown. METHODS AND RESULTS: To identify RBPs that bind to insulin mRNA we performed mass spectrometry analysis on proteins that bound synthetic oligonucloetides mimicing the 5'- and the 3'-untranslated regions (UTRs) of rat and human insulin mRNA in vitro. We observed that the RBPs heterogeneous nuclear ribonucleoprotein (hnRNP) U, polypyrimidine tract binding protein (PTB), hnRNP L and T-cell restricted intracellular antigen 1-related protein (TIA-1-related protein; TIAR) bind to insulin mRNA sequences, and that the in vitro binding affinity of these RBPs changed when INS-1 cells were exposed to glucose, 3-isobutyl-1-methylxanthine (IBMX) or nitric oxide...
September 2016: Heliyon
https://www.readbyqxmd.com/read/27689010/knockdown-of-atp-citrate-lyase-in-pancreatic-beta-cells-does-not-inhibit-insulin-secretion-or-glucose-flux-and-implicates-the-acetoacetate-pathway-in-insulin-secretion
#17
Mahmoud El Azzouny, Melissa J Longacre, Israr-Ul H Ansari, Robert T Kennedy, Charles F Burant, Michael J MacDonald
OBJECTIVE: Glucose-stimulated insulin secretion in pancreatic beta cells requires metabolic signals including the generation of glucose-derived short chain acyl-CoAs in the cytosol from mitochondrially-derived metabolites. One concept of insulin secretion is that ATP citrate lyase generates short chain acyl-CoAs in the cytosol from mitochondrially-derived citrate. Of these, malonyl-CoA, is believed to be an important signal in insulin secretion. Malonyl-CoA is also a precursor for lipids...
October 2016: Molecular Metabolism
https://www.readbyqxmd.com/read/27687546/wnt4-antagonises-wnt3a-mediated-increases-in-growth-and-glucose-stimulated-insulin-secretion-in-the-pancreatic-beta-cell-line-ins-1
#18
A Bowen, K Kos, J Whatmore, S Richardson, H J Welters
The Wnt signalling pathway in beta-cells has been linked to the development of type 2 diabetes. Investigating the impact of a non-canonical Wnt ligand, Wnt4, on beta-cell function we found that in INS-1 cells, Wnt4 was able to completely block Wnt3a stimulated cell growth and insulin secretion. However, despite high levels of Wnt4 protein being detected in INS-1 cells, reducing the expression of Wnt4 had no impact on cell growth or Wnt3a signalling. As such, the role of the endogenously expressed Wnt4 in beta-cells is unclear, but the data showing that Wnt4 can act as a negative regulator of canonical Wnt signalling in beta-cells suggests that this pathway could be a potential target for modulating beta-cell function...
October 28, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27684825/atorvastatin-inhibits-insulin-synthesis-by-inhibiting-the-ras-raf-erk-creb-pathway-in-ins-1-cells
#19
Hongxi Sun, Yu Li, Bei Sun, Ningning Hou, Juhong Yang, Miaoyan Zheng, Jie Xu, Jingyu Wang, Yi Zhang, Xianwei Zeng, Chunyan Shan, Bai Chang, Liming Chen, Baocheng Chang
BACKROUND: Type 2 diabetes has become a global epidemic disease. Atorvastatin has become a cornerstone in the prevention and treatment of atherosclerosis. However, increasing evidence showed that statins can dose-dependently increase the risk of diabetes mellitus. The mechanism is not clear. OBJECTIVE: The Ras complex pathway (Ras/Raf/extracellular signal-regulated kinase [ERK]/cAMP response element-binding protein [CREB]) is the major pathway that regulates the gene transcription...
September 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27667109/-endoplasmic-reticulum-stress-in-ins-1-3-cell-associated-with-the-expression-changes-of-mody-gene-pathway
#20
Y T Liu, S R Li, Z Wang, J Z Xiao
Objective: To profile the gene expression changes associated with endoplasmic reticulum stress in INS-1-3 cells induced by thapsigargin (TG) and tunicamycin (TM). Methods: Normal cultured INS-1-3 cells were used as a control. TG and TM were used to induce endoplasmic reticulum stress in INS-1-3 cells. Digital gene expression profiling technique was used to detect differentially expressed gene. The changes of gene expression were detected by expression pattern clustering analysis, gene ontology (GO) function and pathway enrichment analysis...
September 13, 2016: Zhonghua Yi Xue za Zhi [Chinese medical journal]
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