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https://www.readbyqxmd.com/read/28631500/pancreatic-%C3%AE-cell-survival-and-proliferation-are-promoted-by-protein-kinase-g-type-i%C3%AE-and-downstream-regulation-of-akt-foxo1
#1
Janica C Wong, Van Vo, Priyatham Gorjala, Ronald R Fiscus
Early studies showed nitric oxide as a pro-inflammatory-cytokine-induced toxin involved in pancreatic β-cell destruction during pathogenesis of type-1 diabetes. However, nitric oxide has both cytotoxic and cytoprotective effects on mammalian cells, depending on concentration and micro-environmental surroundings. Our studies have shown that low/physiological-level nitric oxide selectively activates protein kinase G type Iα isoform, promoting cytoprotective/pro-cell-survival effects in many cell types. In bone marrow-derived stromal/mesenchymal stem cells, protein kinase G type Iα mediates autocrine effects of nitric oxide and atrial natriuretic peptide, promoting DNA-synthesis/proliferation and cell survival...
June 1, 2017: Diabetes & Vascular Disease Research
https://www.readbyqxmd.com/read/28626000/baiap3-a-c2-domain-containing-munc13-protein-controls-the-fate-of-dense-core-vesicles-in-neuroendocrine-cells
#2
Xingmin Zhang, Shan Jiang, Kelly A Mitok, Lingjun Li, Alan D Attie, Thomas F J Martin
Dense-core vesicle (DCV) exocytosis is a SNARE (soluble N-ethylmaleimide-sensitive fusion attachment protein receptor)-dependent anterograde trafficking pathway that requires multiple proteins for regulation. Several C2 domain-containing proteins are known to regulate Ca(2+)-dependent DCV exocytosis in neuroendocrine cells. In this study, we identified others by screening all (∼139) human C2 domain-containing proteins by RNA interference in neuroendocrine cells. 40 genes were identified, including several encoding proteins with known roles (CAPS [calcium-dependent activator protein for secretion 1], Munc13-2, RIM1, and SYT10) and many with unknown roles...
June 16, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28593826/exposure-to-static-magnetic-fields-increases-insulin-secretion-in-rat-ins-1-cells-by-activating-the-transcription-of-the-insulin-gene-and-up-regulating-the-expression-of-vesicle-secreted-proteins
#3
Libin Mao, Huiqin Wang, Fenghui Ma, Zhixia Guo, Hongpeng He, Hao Zhou, Nan Wang
PURPOSE: To evaluate the effect of static magnetic fields (SMFs) on insulin secretion and explore the mechanisms underlying exposure to SMF-induced insulin secretion in rat insulinoma INS-1 cells. MATERIALS AND METHODS: INS-1 cells were exposed to a 400 mT SMF for 72 h, and the proliferation of INS-1 cells was detected by (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The secretion of insulin was measured with an enzyme linked immunosorbent assays (ELISA), the expression of genes was detected by real-time PCR, and the expression of proteins was measured by Western blotting...
June 13, 2017: International Journal of Radiation Biology
https://www.readbyqxmd.com/read/28587345/palmitoleate-inhibits-insulin-transcription-by-activating-the-erk1-2-pathway-in-rat-pancreatic-%C3%AE-cells
#4
Yumei Yang, Liangliang Gong
The aim of the present study was to evaluate the effects of palmitoleate on insulin secretion and insulin mRNA levels, and to investigate the transcriptional regulation of insulin. INS-1 rat insulinoma cells were treated with palmitoleate in the presence of high glucose, and the amount of secreted insulin was measured via radioimmunoassay. Reverse transcription-quantitative polymerase chain reaction was performed to evaluate the mRNA levels of insulin and pancreatic and duodenal homeobox 1 (PDX1) under palmitoleate treatment...
June 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28570746/influence-of-extremely-low-frequency-magnetic-fields-on-ca-2-signaling-and-double-messenger-system-in-mice-hippocampus-and-reversal-function-of-procyanidins-extracted-from-lotus-seedpod
#5
Haihui Zhang, Yuanyuan Dai, Yanxiang Cheng, Yuanqing He, Zandile Manyakara, Yuqing Duan, Guibo Sun, Xiaobo Sun
This research investigated the influence of extremely low frequency magnetic fields (ELF-MF; 50 Hz, 8 mT, 4 h per day, for 28 days) on calcium ion signaling and the double messenger system in the hippocampus of mice. Messengers that were studied included: G-protein, Ins(1,4,5)P3 (IP3 ), diacylglycerol (DAG), cAMP-dependent protein kinase (PKA), and Ca(2+) -dependent protein kinase C (PKC). The results showed that ELF-MF caused an increase in the levels of Gi protein, IP3, DAG, PKA and PKC beta, calcium and calmodulin-dependent protein phosphatase calcineuring (PP2B), and intracellular Ca(2+) content, and a decrease in calcium/calmodulin-dependent protein kinase II (CaMK II) and PKC alpha...
June 1, 2017: Bioelectromagnetics
https://www.readbyqxmd.com/read/28554270/dephosphorylation-of-myo-inositol-phosphates-in-the-in-vitro-intestinal-caco-2-cell-model
#6
Karlis Briviba, Margit Schollenberger, Markus Rodehutscord, Ralf Greiner
Plant and microbial phytases present in raw materials can cause a dephosphorylation of phytate (myo-inositol hexakisphosphate) (InsP6)) during food processing resulting in a broad range of different myo-inositol phosphates such as pentakisphosphate (InsP5) and tetrakisphosphate (InsP4) in foods. Here, we investigated whether the human intestinal epithelium is able to dephosphorylate myo-inositol phosphates (InsP6, InsP5-, InsP4-, InsP3-isomers) using an in vitro model with differentiated human Caco-2 cells cultured on semipermeable inserts...
May 30, 2017: International Journal of Food Sciences and Nutrition
https://www.readbyqxmd.com/read/28551552/standardized-mori-ramulus-extract-improves-insulin-secretion-and-insulin-sensitivity-in-c57blks-j-db-db-mice-and-ins-1-cells
#7
Soo-Yeon Park, Bora Jin, Jae-Ho Shin, Sirichai Adisakwattana, Oran Kwon
Abnormalities in the hyperbolic relationship between insulin sensitivity and insulin secretion may cause oxidative stress and non-enzymatic glycation, resulting in an increased risk of type 2 diabetes. Here, we performed a 14-week study to investigate the effects of ethanolic extract of Mori ramulus (MRE; 0, 800, and 1600mg/kg body weight) and its signature component oxyresveratrol (OXY; 800mg/kg body weight) on β-cell dysfunction and insulin resistance in C57BLKS/J db/db mice fed with a high-fat diet. Compared with the diabetic control group, the high-dose MRE group showed a significant decrease in fasting blood glucose (p=0...
May 25, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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/28534945/trb3-mediates-advanced-glycation-end-product-induced-apoptosis-of-pancreatic-%C3%AE-cells-through-the-protein-kinase-c-%C3%AE-pathway
#9
Meng Wang, Wenjian Zhang, Shiqing Xu, Liang Peng, Zai Wang, Honglin Liu, Qing Fang, Tingting Deng, Xiuli Men, Jinning Lou
Advanced glycation end products (AGEs), which accumulate in the body during the development of diabetes, may be one of the factors leading to pancreatic β-cell failure and reduced β-cell mass. However, the mechanisms responsible for AGE‑induced apoptosis remain unclear. This study identified the role and mechanisms of action of tribbles homolog 3 (TRB3) in AGE-induced β-cell oxidative damage and apoptosis. Rat insulinoma cells (INS-1) were treated with 200 µg/ml AGEs for 48 h, and cell apoptosis was then detected by TUNEL staining and flow cytometry...
May 16, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28512156/effects-of-metformin-on-compensatory-pancreatic-%C3%AE-cell-hyperplasia-in-mice-fed-a-high-fat-diet
#10
Kazuki Tajima, Jun Shirakawa, Tomoko Okuyama, Mayu Kyohara, Shunsuke Yamazaki, Yu Togashi, Yasuo Terauchi
Metformin has been widely used for the treatment of type 2 diabetes. However, the effect of metformin on pancreatic β-cells remains controversial. In this study, we investigated the impacts of treatment with metformin on pancreatic β-cells in a mouse model fed a high-fat diet (HFD), which triggers adaptive β-cell replication. An 8-week treatment with metformin improved insulin resistance and suppressed the compensatory β-cell hyperplasia induced by HFD-feeding. In contrast, the increment in β-cell mass arising from 60 weeks of HFD-feeding was similar in mice treated with and those treated without metformin...
May 16, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28496188/preclinical-evaluation-of-pac1-targeting-with-radiolabeled-maxadilan
#11
Lieke Joosten, Maarten Brom, Martin K H Schäfer, Otto C Boerman, Eberhard Weihe, Martin Gotthardt
There is an ongoing search for new tracers to optimize imaging of beta cell-derived tumors (insulinomas). The PAC1 receptor, expressed by insulinomas, can be used for targeting of these tumors. Here, we investigated whether radiolabeled maxadilan could be used for insulinoma imaging. Maxadilan was C- or N-terminally conjugated with DTPA (termed maxadilan-DPTA or DTPA-maxadilan respectively). BALB/c nude mice bearing subcutaneous INS-1 tumors were injected with either In-111-labeled maxadilan-DTPA or In-111-DTPA-maxadilan...
May 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28488455/intracellular-methylglyoxal-induces-oxidative-damage-to-pancreatic-beta-cell-line-ins-1-cell-through-ire1%C3%AE-jnk-and-mitochondrial-apoptotic-pathway
#12
Chongxiao Liu, Yanhong Huang, Yifan Zhang, Xueru Chen, Xiang Kong, Yan Dong
An increased intracellular methylglyoxal (MGO) under hyperglycemia led to pancreatic beta cell death. However, its mechanism in which way with MGO induced beta cell death remains unknown. We investigated both high glucose and MGO treatment significantly inclined intracellular MGO concentration and inhibited cell viability in vitro. MGO treatment also triggered intracellular advanced glycation end products (AGEs) formation, declined mitochondrial membrane potential (MMP), increased oxidative stress and the expression of ER stress mediators Grp78/Bip and p-PERK; activated mitochondrial apoptotic pathway, which could mimic by Glo1 knockdown...
May 10, 2017: Free Radical Research
https://www.readbyqxmd.com/read/28487119/the-mammalian-ste20-like-kinase-1-mst1-is-a-substrate-for-the-apoptosis-inhibiting-protein-kinase-ck2
#13
Christina Servas, Sandra Kiehlmeier, Julia Hach, Rebecca Gross, Claudia Götz, Mathias Montenarh
Apoptosis and the response to cell stress are evolutionary highly conserved mechanisms. Both processes require strict regulation, which is often performed by protein kinases. The mammalian Sterile 20-like kinase 1 (MST1) is a pro-apoptotic protein kinase, which is activated and cleaved by caspases upon the induction of cell stress. Being a phosphoprotein itself, the activity of MST1 is regulated by phosphorylation. Protein kinase CK2 is an anti-apoptotic protein kinase which seems to be involved in the regulation of many different cellular processes including apoptosis...
May 6, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28457895/an-approach-for-half-life-extension-and-activity-preservation-of-an-anti-diabetic-peptide-drug-based-on-genetic-fusion-with-an-albumin-binding-aptide
#14
Daejin Kim, Hyungsu Jeon, Sukyung Ahn, Won Il Choi, Sunghyun Kim, Sangyong Jon
Although the peptide, exenatide, has been widely used as a drug for the treatment of type 2 diabetes, its short plasma half-life requires frequent subcutaneous injection, resulting in poor patient compliance in addition to side effects such as infection at the sites of injection. Here, we report a novel long-acting fusion peptide comprising exenatide and a human serum albumin (HSA)-binding aptide. A phage display screen of a library of aptides, yielded an HSA-specific aptide (APTHSA) that bound HSA with a Kd of 188nM...
June 28, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28445528/baicalein-protects-rat-insulinoma-ins-1-cells-from-palmitate-induced-lipotoxicity-by-inducing-ho-1
#15
Hyun Jeong Kwak, Dongki Yang, Yongha Hwang, Hee-Sook Jun, Hyae Gyeong Cheon
OBJECTIVE: β-Cell dysfunction plays a central role in the pathogenesis of type 2 diabetes (T2D), and the identification of novel approaches to improve β-cell function is essential to treat this disease. Baicalein, a flavonoid originally isolated from the root of Scutellaria Baicalensis, has been shown to have beneficial effects on β-cell function. Here, the authors investigated the molecular mechanism responsible for the protective effects of baicalein against palmitate (PA)-induced impaired β-cell function, and placed focus on the role of heme oxygenase (HO)-1...
2017: PloS One
https://www.readbyqxmd.com/read/28438776/the-immunoproteasome-is-induced-by-cytokines-and-regulates-apoptosis-in-human-islets
#16
Morten Lundh, Marco Bugliani, Tina Dahlby, Danny Hung-Chieh Chou, Bridget Wagner, Seyed Mojtaba Ghiasi, Vincenzo De Tata, Zhifei Chen, Marianne Nissen Lund, Michael J Davies, Piero Marchetti, Thomas Mandrup-Poulsen
In addition to degrading misfolded and damaged proteins, the proteasome regulates the fate of cells in response to stress. The role of the proteasome in pro-inflammatory cytokine-induced human beta-cell apoptosis is unknown. INS-1, INS-1E and human islets were exposed to combinations of IFNγ, IL-1β and TNFα with or without addition of small molecules. Gene expression was assessed by microarray or quantitative PCR. Proteasome activities were analyzed using luminescent assays. Protein oxidation, Western blotting and electron microscopy were used to examine mechanisms underlying cytokine-induced apoptosis...
April 24, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28432716/deciphering-tacrolimus-induced-toxicity-in-pancreatic-%C3%AE-cells
#17
J Triñanes, A E Rodriguez-Rodriguez, Y Brito-Casillas, A Wagner, A P J De Vries, G Cuesto, A Acebes, E Salido, A Torres, E Porrini
β-cell transcription factors like: FoxO1, MafA, PDX-1, NeuroD, are dysfunctional in type 2 diabetes (T2DM). PTDM resembles T2DM and reflects interaction between pre-transplant insulin resistance and immunosuppressants, mainly calcineurin inhibitors. We evaluated the effect of tacrolimus, cyclosporine-A and metabolic stressors (glucose+palmitate) on insulinoma β-cells (INS-1) in vitro and in pancreata of obese and lean Zucker rats. Cells were cultured for five days with 100μM palmitate and 22mM glucose; cyclosporin-A (250ng/mL) or tacrolimus (15ng/mL) were added the last 48h...
April 22, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28428639/obestatin-stimulates-glucose-induced-insulin-secretion-through-ghrelin-receptor-ghs-r
#18
Geetali Pradhan, Chia-Shan Wu, Jong Han Lee, Preeti Kanikarla, Shaodong Guo, Vijay K Yechoor, Susan L Samson, Yuxiang Sun
Orexigenic hormone ghrelin and anorexic hormone obestatin are encoded by the same preproghrelin gene. While it is known that ghrelin inhibits glucose-stimulated insulin secretion (GSIS), the effect of obestatin on GSIS is unclear. Ghrelin's effect is mediated by its receptor Growth Hormone Secretagogue Receptor (GHS-R), but the physiologically relevant receptor of obestatin remains debatable. Here we have investigated the effect of obestatin on GSIS in vitro, in vivo and ex vivo, and tested whether obestatin regulates insulin secretion through GHS-R...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28422431/effect-of-empagliflozin-on-tacrolimus-induced-pancreas-islet-dysfunction-and-renal-injury
#19
J Jin, L Jin, K Luo, S W Lim, B H Chung, C W Yang
An inhibitor of sodium glucose co-transporter type 2 (SGLT-2) is recommended in type 2 diabetes mellitus (DM) but its use is still undetermined in tacrolimus (TAC)-induced DM. We evaluated the effect of empagliflozin (Em) on TAC-induced pancreatic islet dysfunction and renal injury in an experimental model of TAC-induced DM and in vitro. TAC induced a twofold increase in SGLT-2 expression, while Em decreased SGLT-2 expression and further increased urinary glucose excretion compared to the TAC group. Em reduced hyperglycemia and increased plasma insulin level, pancreatic islet size, and glucose-stimulated insulin secretion compared to the TAC group...
April 19, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28406517/biochemical-studies-of-inositol-n-acetylglucosaminyltransferase-involved-in-mycothiol-biosynthesis-in-corynebacterium-diphtheria
#20
Yuchuan Guo, Lizhen Wang, Jiatong Guo, Guofeng Gu, Zhongwu Guo
Mycothiol (MSH) is the predominant low molecular weight thiol produced by actinomycetes, and it plays a pivotal role in the bacterial detoxication process. 1L-myo-Inositol-1-phosphate (1L-Ins-1-P) α-N-acetylglucosaminyltransferase (GlcNAc-T), known as MshA, is the only glycosyltransferase involved in MSH biosynthesis. In this work, the MshA from Corynebacterium diphtheria, named as CdMshA, was expressed, purified, and studied in detail. Its enzymatic activity to transfer GlcNAc to 1L-Ins-1-P was confirmed by the isolation and rigorous characterization of its reaction product 3-phospho-1-d-myo-inositol-2-acetamido-2-deoxy-α-d-glucopyranoside...
May 3, 2017: Organic & Biomolecular Chemistry
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