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https://www.readbyqxmd.com/read/28432716/deciphering-tacrolimus-induced-toxicity-in-pancreatic-%C3%AE-cells
#1
J Triñanes, A E Rodriguez-Rodriguez, Y Brito, 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
#2
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
#3
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 experimental model of TAC-induced DM and in vitro. TAC induced a two-fold 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 (GSIS) 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
#4
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...
April 13, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28406239/cmd-05-a-novel-promising-clinical-anti-diabetic-drug-candidate-in-vivo-and-vitro-studies
#5
Jie Ma, Huan Li, Xiangnan Hu, Lu Yang, Qi Chen, Congli Hu, Zhihao Chen, Xiaoyan Tian, Yang Yang, Ying Luo, Run Gan, Junqing Yang
Dipeptidyl peptidase IV (DPP-IV) inhibitor has been expected to be a new class of anti-diabetic agent. The present study was designed to characterize the pharmacological profiles of CMD-05, a novel DPP-IV inhibitor discovered in our laboratory, in vitro and in vivo. The IC50 of CMD-05 on DPP-IV inhibitory activity was approximately 12 nM while vildagliptin was 3.5 nM in vitro. In diabetes rat model established by high fat diet/low dose streptozotocin, CMD-05 inhibited DPP-IV activity, significantly improved glucose tolerance, increased GLP-1 and insulin levels in plasma...
April 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28405188/compound-19e-a-novel-glucokinase-activator-protects-against-cytokine-induced-beta-cell-apoptosis-in-ins-1-cells
#6
Yoon Sin Oh, Eunhui Seo, Kaapjoo Park, Hee-Sook Jun
Previously, compound 19e, a novel heteroaryl-containing benzamide derivative, was identified as a potent glucokinase activator (GKA) and showed a glucose-lowering effect in diabetic mice. In this study, the anti-apoptotic actions of 19e were evaluated in INS-1 pancreatic beta-cells co-treated with TNF-α and IL-1β to induce cell death. Compound 19e protected INS-1 cells from cytokine-induced cell death, and the effect was similar to treatment with another GKA or exendin-4. Compound 19e reduced annexin-V stained cells and the expression of cleaved caspase-3 and poly (ADP-ribose) polymerase protein, as well as upregulated the expression of B-cell lymphoma-2 protein...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28397263/protective-effect-of-cirsimaritin-against-streptozotocin-induced-apoptosis-in-pancreatic-beta-cells
#7
Dahae Lee, Ki Hyun Kim, Jaemin Lee, Gwi Seo Hwang, Hye Lim Lee, Dae-Hyun Hahm, Chang Ki Huh, Sang Cheon Lee, Sanghyun Lee, Ki Sung Kang
OBJECTIVES: Maintaining glucose homoeostasis is essential for the survival of cells. Despite the various health benefits of Korean thistle (Cirsium japonicum var. maackii), their effects on pancreatic β-cell apoptosis in type 1 diabetes mellitus and the underlying mechanisms remain unclear, and experimentally investigated in this study. METHODS: The effects of C. japonicum var. maackii and its active component cirsimaritin against streptozotocin (STZ)-induced cytotoxicity were assessed in INS-1 cells...
April 11, 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/28394923/effects-and-underlying-mechanisms-of-irisin-on-the-proliferation-and-apoptosis-of-pancreatic-%C3%AE-cells
#8
Shiwei Liu, Fang Du, Xin Li, Mingming Wang, Ruixue Duan, Jiaxin Zhang, Yaru Wu, Qi Zhang
Pancreatic β cell dysfunction and reduction due to glucose toxicity play a crucial role in the development of type 2 diabetes mellitus (T2DM). Irisin, a novel exercise-induced myokine, reduces obesity, improves insulin resistance and lowers blood glucose by promoting the browning of white adipose tissue, thereby enhancing thermogenesis and increasing energy expenditure. Recent studies have reported that irisin promotes cell proliferation and protects cells from apoptosis. However, the effects of irisin on pancreatic β cells are unknown...
2017: PloS One
https://www.readbyqxmd.com/read/28363490/geniposide-improves-insulin-production-and-reduces-apoptosis-in-high-glucose-induced-glucotoxic-insulinoma-cells
#9
L X Guo, J H Liu, X X Zheng, Z Y Yin, J Kosaraju, K Y Tam
Our previous work revealed that in the pancreatic β cell line, geniposide modulated ATP production and glucose-stimulated insulin secretion (GSIS) induced by the acute stimulation of high glucose concentration. However, the effects of geniposide on functional impairment and the mass of β-cells exposed to elevated levels of glucose remains unknown. In the present study, impaired GSIS and restrained proliferation were observed in the prolonged culture of insulinoma INS-1 cells with 33mM of glucose (high glucose)...
March 28, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28356733/a-novel-selective-vpac2-agonist-peptide-conjugated-chitosan-modified-selenium-nanoparticles-with-enhanced-anti-type-2-diabetes-synergy-effects
#10
Shao-Jun Zhao, De-Hua Wang, Yan-Wei Li, Lei Han, Xing Xiao, Min Ma, David Chi-Cheong Wan, An Hong, Yi Ma
A novel neuroendocrine peptide, pituitary adenylate cyclase activating peptide (PACAP), was found to have an important role in carbohydrate or lipid metabolism and was susceptible to dipeptidyl peptidase IV degradation. It can not only mediate glucose-dependent insulin secretion and lower blood glucose by activating VPAC2 receptor, but also raise blood glucose by promoting glucagon production by VPAC1 receptor activation. Therefore, its therapeutic application is restricted by the exceedingly short-acting half-life and the stimulatory function for glycogenolysis...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28356096/%C3%AE-cell-protection-and-antidiabetic-activities-of-crassocephalum-crepidioides-asteraceae-benth-s-moore-extract-against-alloxan-induced-oxidative-stress-via-regulation-of-apoptosis-and-reactive-oxygen-species-ros
#11
Entaz Bahar, Kazi-Marjahan Akter, Geum-Hwa Lee, Hwa-Young Lee, Harun-Or Rashid, Min-Kyung Choi, Kashi Raj Bhattarai, Mir Mohammad Monir Hossain, Joushan Ara, Kishor Mazumder, Obayed Raihan, Han-Jung Chae, Hyonok Yoon
BACKGROUND: Medicinal plants are becoming more popular in the treatment of various diseases because of the adverse effects of the current therapy, especially antioxidant plant components such as phenols and flavonoids have a protective role against oxidative stress-induced degenerative diseases like diabetes. Thus, the purpose of this study was to investigate β-cell protection and antidiabetic activities of Crassocephalum crepidioides (Asteraceae) Benth. S. Moore. METHOD: The in-vitro study was conducted by the pancreatic β-cell culture and α-amylase inhibition technique which includes two methods, namely starch-iodine method and 3,5-dinitrosalicylic acid (DNSA) method...
March 29, 2017: BMC Complementary and Alternative Medicine
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
#12
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
#13
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
#14
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
#15
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
#16
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...
May 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
#17
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 12, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28280903/microrna-21-targets-bcl2-mrna-to-increase-apoptosis-in-rat-and-human-beta-cells
#18
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
#19
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
#20
Chunyan Liu, Yanan 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...
May 2017: Cell Biology International
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