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https://www.readbyqxmd.com/read/28346520/downregulation-of-mir-139-5p-contributes-to-the-antiapoptotic-effect-of-liraglutide-on-the-diabetic-rat-pancreas-and-ins-1-cells-by-targeting-irs1
#1
Jin Li, Lei Su, Ying-Ying Gong, Mei-Lin Ding, Shu-Bin Hong, Shuang Yu, Hai-Peng Xiao
Liraglutide is administered as glucagon-like peptide-1 (GLP-1) receptor agonist for diabetic patients and can protect pancreatic β-cells by inhibiting their apoptosis. MicroRNA-139-5p (miRNA-139-5p) participates in the regulation of cancer cell apoptosis. However, it is not clear whether miR-139-5p contributes to the anti-apoptotic effect of liraglutide in β-cells. The objective of the present study was to investigate the role of miR-139-5p on apoptosis of pancreatic β-cells. MicroRNA levels in pancreatic tissue from diabetic rats and INS-1 cells treated with liraglutide were measured by real-time quantitative RT-PCR...
2017: PloS One
https://www.readbyqxmd.com/read/28338182/microrna-199a-5p-mediates-high-glucose-induced-reactive-oxygen-species-production-and-apoptosis-in-ins-1-pancreatic-%C3%AE-cells-by-targeting-sirt1
#2
N Lin, X-Y Li, H-M Zhang, Z Yang, Q Su
OBJECTIVE: Hyperglycemia-induced pancreatic β-cell loss is a pathologic hallmark of type 2 diabetes mellitus (T2DM). This study was conducted to clarify the function of microRNA (miR)-199a-5p in high glucose-elicited β-cell toxicity and associated molecular mechanisms. MATERIALS AND METHODS: INS-1 rat pancreatic β-cells were cultured under normal (11 mM) or high (30 mM) glucose for 16-72 h and examined for miR-199a-5p expression. Gain and loss-of-function studies were performed to determine the role of miR-199a-5p in high glucose-induced apoptosis and reactive oxygen species (ROS) production...
March 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28336918/clinically-applicable-gaba-receptor-positive-allosteric-modulators-promote-%C3%A3-cell-replication
#3
Jide Tian, Hoa Dang, Blake Middleton, Daniel L Kaufman
A key goal of diabetes research is to develop treatments to safely promote human ß-cell replication. It has recently become appreciated that activation of γ-aminobutyric acid receptors (GABA-Rs) on ß-cells can promote their survival and replication. A number of positive allosteric modulators (PAMs) that enhance GABA's actions on neuronal GABAA-Rs are in clinical use. Repurposing these GABAA-R PAMs to help treat diabetes is theoretically appealing because of their safety and potential to enhance the ability of GABA, secreted from ß-cells, or exogenously administered, to promote ß-cell replication and survival...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28332581/elevated-mir-130a-mir130b-mir-152-expression-reduces-intracellular-atp-levels-in-the-pancreatic-beta-cell
#4
Jones K Ofori, Vishal A Salunkhe, Annika Bagge, Neelanjan Vishnu, Mototsugu Nagao, Hindrik Mulder, Claes B Wollheim, Lena Eliasson, Jonathan L S Esguerra
MicroRNAs have emerged as important players of gene regulation with significant impact in diverse disease processes. In type-2 diabetes, in which impaired insulin secretion is a major factor in disease progression, dysregulated microRNA expression in the insulin-secreting pancreatic beta cell has been widely-implicated. Here, we show that miR-130a-3p, miR-130b-3p, and miR-152-3p levels are elevated in the pancreatic islets of hyperglycaemic donors, corroborating previous findings about their upregulation in the islets of type-2 diabetes model Goto-Kakizaki rats...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28318577/effect-of-dietary-mineral-phosphorus-and-phytate-on-in-situ-ruminal-phytate-disappearance-from-different-concentrates-in-dairy-cows
#5
E Haese, J Möhring, H Steingass, M Schollenberger, M Rodehutscord
The first objective of this study was to determine the influence of dietary composition on the in situ disappearance of phytate (InsP6) from wheat, corn, soybean meal, and rapeseed meal [solvent-extracted, without (RSM) or with (hRSM) heat treatment] in the rumen of dairy cows. The second objective was to assess the primary degradation products of InsP6 in the rumen. Three diets differing in phosphorus and InsP6 concentration (basal diet = 0.38% P in dry matter; high-P diet = 0.56% P; high-InsP6 diet = 0.39% P) were fed to 3 ruminally fistulated lactating Jersey cows in a 3 × 3 Latin square...
March 16, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28300567/9-cis-retinoic-acid-modulates-myotrophin-expression-and-its-mir-in-physiological-and-pathophysiological-cell-models
#6
Mariarita Perri, Maria Cristina Caroleo, Nannan Liu, Luca Gallelli, Giovambattista De Sarro, Hiroyuki Kagechika, Erika Cione
Functional studies indicate that essential cellular processes are controlled by Vitamin A derivatives. Among these the retinoic acid isoforms, all-trans- and 9-cis (9cRA), regulate the expression of various genes in both physiological and pathological conditions. Using several in vitro experimental models such as pancreatic β-cells, pre-adipocytes and breast cancer cells with different phenotypes, we demonstrated the capability of 9cRA to modulate myotrophin (Mtpn) and miR-375 expressions. The 9cRA effect in pancreatic β-cells line INS-1 832/13 point out a decreased expression of Mptn at both mRNA and protein levels associated to a concomitant increase of miR-375...
March 11, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28280903/microrna-21-targets-bcl2-mrna-to-increase-apoptosis-in-rat-and-human-beta-cells
#7
Emily K Sims, Alexander J Lakhter, Emily Anderson-Baucum, Tatsuyoshi Kono, Xin Tong, Carmella Evans-Molina
AIMS/HYPOTHESIS: The role of beta cell microRNA (miR)-21 in the pathophysiology of type 1 diabetes has been controversial. Here, we sought to define the context of beta cell miR-21 upregulation in type 1 diabetes and the phenotype of beta cell miR-21 overexpression through target identification. METHODS: Islets were isolated from NOD mice and mice treated with multiple low doses of streptozotocin, as a mouse model of diabetes. INS-1 832/13 beta cells and human islets were treated with IL-1β, IFN-γ and TNF-α to mimic the milieu of early type 1 diabetes...
March 9, 2017: Diabetologia
https://www.readbyqxmd.com/read/28263293/advanced-oxidation-protein-products-promote-nadph-oxidase-dependent-%C3%AE-cell-destruction-and-dysfunction-through-the-bcl-2-bax-apoptotic-pathway
#8
Min Liang, Aiqing Li, Aiju Lou, Xifang Zhang, Youyuan Chen, Lei Yang, Yumin Li, Shenglin Yang, Fan Fan Hou
The accumulation of plasma advanced oxidation protein products (AOPPs) has been linked with diverse disorders, including diabetes, chronic kidney disease, obesity, and metabolic syndrome. The aim of the present study was to evaluate the pathophysiological relevance of AOPPs in β-cell destruction and dysfunction. Exposure of cultured rat β-cells (INS-1) to AOPPs induced an increase in Bax expression, caspase-3 activity, and apoptosis as well as a decrease in Bcl-2 expression in a dose- and time-dependent manner...
March 6, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28244615/geniposide-protects-pancreatic-%C3%AE-cells-from-high-glucose-mediated-injury-by-activation-of-amp-activated-protein-kinase
#9
Chunyan Liu, Yanan Cui, Shuting Hao, Fei Yin, Yonglan Zhang, Jianhui Liu
Our previous works indicated that geniposide could regulate glucose-stimulated insulin secretion (GSIS), and improved chronic high glucose-induced dysfunctions in pancreatic β cells, but the molecular mechanisms remain largely unknown. In the present study, we investigated the role of 5 -AMP-activated protein kinase (AMPK) in high glucose induced cell injury and explored the associated molecular mechanisms in rat INS-1 pancreatic β cells. Data suggested that geniposide obviously prevented the cell damage induced by high (25 mM) glucose in INS-1 cells, which increased the protein levels of cell apoptosis-associated enzymes, including heme oxygenase-1 (HO-1) and Bcl-2, but apparently attenuated the protein level of Bax, an apoptotic protein...
February 28, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28237718/endogenous-beta-cell-cart-regulates-insulin-secretion-and-transcription-of-beta-cell-genes
#10
L Shcherbina, A Edlund, J L S Esguerra, M Abels, Y Zhou, E Ottosson-Laakso, C B Wollheim, O Hansson, L Eliasson, N Wierup
Impaired beta-cell function is key to the development of type 2 diabetes. Cocaine- and amphetamine-regulated transcript (CART) is an islet peptide with insulinotropic and glucagonostatic properties. Here we studied the role of endogenous CART in beta-cell function. CART silencing in INS-1 (832/13) beta-cells reduced insulin secretion and production, ATP levels and beta-cell exocytosis. This was substantiated by reduced expression of several exocytosis genes, as well as reduced expression of genes important for insulin secretion and processing...
February 22, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28230965/fluorine-functionalized-graphene-quantum-dots-as-inhibitor-against-hiapp-amyloid-aggregation
#11
Maryam Yousaf, Huan Huang, Ping Li, Chen Wang, Yanlian Yang
Fibrillar deposits of the human islet amyloid polypeptide (hIAPP) is considered as a root of Type II diabetes mellitus. Fluorinated graphene quantum dots (FGQDs) are new carbon nanomaterials with unique physicochemical properties containing highly electronegative F atoms. Herein we report a single step synthesis method of FGQDs with an inhibitory effect on aggregation and cytotoxicity of hIAPP in vitro. Highly fluorescent and water dispersible FGQDs, less than 3 nm in size were synthesized by the microwave-assisted hydrothermal method...
February 23, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28222044/endocrine-system-on-chip-for-a-diabetes-treatment-model
#12
Dao Thi Thuy Nguyen, Danny van Noort, In-Kyung Jeong, Sungsu Park
The endocrine system is a collection of glands producing hormones which, among others, regulates metabolism, growth and development. One important group of endocrine diseases is diabetes, which is caused by a deficiency or diminished effectiveness of endogenous insulin. By using a microfluidic perfused 3D cell-culture chip, we developed an 'endocrine system on chip' to potentially be able to screen drugs for the treatment of diabetes by measuring insulin release over time. Insulin-secreting β-cells are located in the pancreas, while L-cells, located in the small intestines, stimulate insulin secretion...
February 21, 2017: Biofabrication
https://www.readbyqxmd.com/read/28220272/exposure-to-chronic-hyperglycemic-conditions-results-in-ras-related-c3-botulinum-toxin-substrate-1-rac1-mediated-activation-of-p53-and-atm-kinase-in-pancreatic-%C3%AE-cells
#13
Vaibhav Sidarala, Anjaneyulu Kowluru
Chronic hyperglycemia (HG) promotes pancreatic islet dysfunction which leads to the onset of T2DM. This study is aimed at defining regulatory roles of Rac1, a small G-protein, in the activation of p53 and ATM kinase in pancreatic β-cells, under the duress of HG conditions. We report significant stimulatory effects of HG (20 mM; 24 h) on p53 activation in INS-1 832/13 cells, normal rodent and human islets. Pharmacological inhibition of Rac1 (EHT1864 or NSC23766) significantly suppressed HG-induced p53 activation in INS-1 832/13 cells and rat islets, suggesting novel roles for this small G-protein in the activation of p53...
February 21, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28212395/delayed-apoptosis-allows-islet-%C3%AE-cells-to-implement-an-autophagic-mechanism-to-promote-cell-survival
#14
Heather L Hayes, Brett S Peterson, Jonathan M Haldeman, Christopher B Newgard, Hans E Hohmeier, Samuel B Stephens
Increased β-cell death coupled with the inability to replicate existing β-cells drives the decline in β-cell mass observed in the progression of both major forms of diabetes. Understanding endogenous mechanisms of islet cell survival could have considerable value for the development of novel strategies to limit β-cell loss and thereby promote β-cell recovery. Insulinoma cells have provided useful insight into β-cell death pathways but observations made in cell lines sometimes fail to translate to primary islets...
2017: PloS One
https://www.readbyqxmd.com/read/28198575/tat-biliverdin-reductase-a-protects-ins-1-cells-from-human-islet-amyloid-polypeptide-induced-cytotoxicity-by-alleviating-oxidative-stress-and-er-stress
#15
Su Jin Lee, Hyung Kyung Kang, Won Sik Eum, Jinseu Park, Soo Young Choi, Hyeok Yil Kwon
Human islet amyloid polypeptide (hIAPP), a major constituent of islet amyloid deposits, induces pancreatic β-cell apoptosis and eventually contributes to β-cell deficit in patients with type 2 diabetes mellitus (T2DM). In this study, Tat-mediated transduction of biliverdin reductase A (BLVRA) was investigated in INS-1 cells to examine whether exogenous supplementation of BLVRA prevented hIAPP-induced apoptosis and dysfunction in insulin secretion in β-cells. Tat-BLVRA fusion protein was efficiently delivered into INS-1 cells in a time- and dose-dependent manner...
February 15, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28173719/exo-mir-15a-transfer-from-the-pancreas-augments-diabetic-complications-by-inducing-oxidative-stress
#16
Tengku Ain Kamalden, Anne M Macgregor-Das, Sangeetha M Kannan, Brittany Dunkerly-Eyring, Nurliza Khaliddin, Zhenhua Xu, Anthony P Fusco, Syatirah Abu Yazib, Rhuen Chiou Chow, Elia J Duh, Marc K Halushka, Charles Steenbergen, Samarjit DAS
AIMS: Mi(cro)RNAs, one type of non-coding RNA, modulate post-transcriptional gene expression in various pathogenic pathways in type-2-diabetes (T2D). Currently, little is known about how miRNAs influence disease pathogenesis by targeting cells at a distance. The purpose of this study was to investigate the role of exosomal miRNAs during T2D. RESULTS: We show that miR-15a is increased in the plasma of diabetic patients, correlating with disease severity. miR-15 plays an important role in insulin production in pancreatic-β-cells...
February 7, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28160851/7-8-dihydroxycoumarin-daphnetin-protects-ins-1-pancreatic-%C3%AE-cells-against-streptozotocin-induced-apoptosis
#17
Ramachandran Vinayagam, Baojun Xu
BACKGROUND AND OBJECTIVE: Daphnetin (7, 8-dihydroxycoumarin), a natural coumarin compound, is known to exhibit antioxidant and anti-inflammatrory effects. However, the underlying mechanisms of its anti-apoptotic and antidiabetic effects yet not been examined. Therefore, the present work studied the anti-apoptotic and anti-diabetic effects of daphnetin by in vitro experiments. METHODS: The rat insulinoma (INS-1) cells were pre-treated with daphnetin at different concentrations (1, 10, 20 and 40µM) for 24h followed by exposition to streptozotocin (STZ) (3mM) for 12h...
January 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28157263/a-phosphoinositide-specific-phospholipase-c-pathway-elicits-stress-induced-ca-2-signals-and-confers-salt-tolerance-to-rice
#18
Li Li, Fawei Wang, Peiwen Yan, Wen Jing, Chunxia Zhang, Jörg Kudla, Wenhua Zhang
In animal cells, phospholipase C (PLC) isoforms predominantly hydrolyze phosphatidylinositol-4,5-biphosphates [PtdIns(4,5)P2 ] into the second messengers diacylglycerol (DAG) and inositol 1,4,5-trisphosphate [Ins(1,4,5)P3 ] to regulate diverse biological processes. By contrast, the molecular mechanisms and physiological significance of PLC signaling in plants still awaits full elucidation. Here, we identified a rice (Oryza sativa cv) PI-PLC, OsPLC1, which preferred to hydrolyze phosphatidylinositol-4-phosphate (PtdIns4P) and elicited stress-induced Ca(2+) signals regulating salt tolerance...
February 3, 2017: New Phytologist
https://www.readbyqxmd.com/read/28115068/the-role-of-oxidative-stress-in-dna-damage-in-pancreatic-%C3%AE-cells-induced-by-di-2-ethylhexyl-phthalate
#19
Yan She, Liping Jiang, Liangliang Zheng, Heming Zuo, Min Chen, Xiance Sun, Qiujuan Li, Chengyan Geng, Guang Yang, Lijie Jiang, Xiaofang Liu
Di(2-ethyhexyl) phthalate (DEHP) is commonly used as a plasticizer, which loosely binds to plastic materials and easily leaches out of these products and enters into the environment. Exposure to DEHP can impair pancreatic beta cells (INS-1 cells)function, which is associated with Insulin Resistance (IR) and type 2 diabetes. However, the mechanism of how DEHP leads to Insulin Resistance is unknown. Our results showed that the cell viability of INS-1 cells exposed to DEHP (0-1600 μM) were decreased in a concentration-dependent manner...
March 1, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28108607/insulin-like-growth-factor-binding-protein-1-could-improve-glucose-regulation-and-insulin-sensitivity-through-its-rgd-domain
#20
Natalie J Haywood, Paul A Cordell, Kar Yeun Tang, Natallia Makova, Nadira Y Yuldasheva, Helen Imrie, Hema Viswambharan, Alexander F Bruns, Richard M Cubbon, Mark T Kearney, Stephen B Wheatcroft
Low circulating levels of insulin-like growth factor binding protein 1 (IGFBP-1) are associated with insulin resistance and predict the development of type 2 diabetes. IGFBP-1 can affect cellular functions independently of IGF binding through an Arg-Gly-Asp (RGD) integrin-binding motif. Whether causal mechanisms underlie the favorable association of high IGFBP-1 levels with insulin sensitivity and whether these could be exploited therapeutically remain unexplored. We used recombinant IGFBP-1 and a synthetic RGD-containing hexapeptide in complementary in vitro signaling assays and in vivo metabolic profiling in obese mice to investigate the effects of IGFBP-1 and its RGD domain on insulin sensitivity, insulin secretion, and whole-body glucose regulation...
February 2017: Diabetes
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