Experimental Diabetes Research最新文献_第3页

Suppression of the nuclear factor Eny2 increases insulin secretion in poorly functioning INS-1E insulinoma cells. 抑制核因子Eny2可增加功能不良的INS-1E胰岛素瘤细胞的胰岛素分泌。

Experimental Diabetes Research Pub Date : 2012-01-01 Epub Date: 2012-05-10 DOI: 10.1155/2012/460869

P Dames, M Weise, R Puff, B Göke, K G Parhofer, J Seissler, A Lechner

{"title":"Suppression of the nuclear factor Eny2 increases insulin secretion in poorly functioning INS-1E insulinoma cells.","authors":"P Dames, M Weise, R Puff, B Göke, K G Parhofer, J Seissler, A Lechner","doi":"10.1155/2012/460869","DOIUrl":"https://doi.org/10.1155/2012/460869","url":null,"abstract":"Eny2, the mammalian ortholog of yeast Sus1 and drosophila E(y)2, is a nuclear factor that participates in several steps of gene transcription and in mRNA export. We had previously found that Eny2 expression changes in mouse pancreatic islets during the metabolic adaptation to pregnancy. We therefore hypothesized that the protein contributes to the regulation of islet endocrine cell function and tested this hypothesis in rat INS-1E insulinoma cells. Overexpression of Eny2 had no effect but siRNA-mediated knockdown of Eny2 resulted in markedly increased glucose and exendin-4-induced insulin secretion from otherwise poorly glucose-responsive INS-1E cells. Insulin content, cellular viability, and the expression levels of several key components of glucose sensing remained unchanged; however glucose-dependent cellular metabolism was higher after Eny2 knockdown. Suppression of Eny2 enhanced the intracellular incretin signal downstream of cAMP. The use of specific cAMP analogues and pathway inhibitors primarily implicated the PKA and to a lesser extent the EPAC pathway. In summary, we identified a potential link between the nuclear protein Eny2 and insulin secretion. Suppression of Eny2 resulted in increased glucose and incretin-induced insulin release from a poorly glucose-responsive INS-1E subline. Whether these findings extend to other experimental conditions or to in vivo physiology needs to be determined in further studies.","PeriodicalId":12109,"journal":{"name":"Experimental Diabetes Research","volume":"2012 ","pages":"460869"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/460869","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30657057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5

Bone: incretin hormones perceiver or receiver? 骨:肠促胰岛素激素的感知者还是接受者?

Experimental Diabetes Research Pub Date : 2012-01-01 Epub Date: 2012-06-17 DOI: 10.1155/2012/519784

Ilaria Dicembrini, Edoardo Mannucci, Carlo Maria Rotella

引用次数: 25

Topical application of Sadat-Habdan mesenchymal stimulating peptide (SHMSP) accelerates wound healing in diabetic rabbits. 局部应用Sadat-Habdan间充质刺激肽(SHMSP)促进糖尿病家兔伤口愈合。

Experimental Diabetes Research Pub Date : 2012-01-01 Epub Date: 2012-06-19 DOI: 10.1155/2012/531961

Abdulmohsen H Al-Elq, Mir Sadat-Ali, Mohamed Elsharawy, Ibrahim Al-Habdan, Fatin Othman Al-Aqeel, Magda M Naim

{"title":"Topical application of Sadat-Habdan mesenchymal stimulating peptide (SHMSP) accelerates wound healing in diabetic rabbits.","authors":"Abdulmohsen H Al-Elq, Mir Sadat-Ali, Mohamed Elsharawy, Ibrahim Al-Habdan, Fatin Othman Al-Aqeel, Magda M Naim","doi":"10.1155/2012/531961","DOIUrl":"https://doi.org/10.1155/2012/531961","url":null,"abstract":"Objective: Diminished wound healing is a common problem in diabetic patients due to diminished angiogenesis. SHMSP was found to promote angiogenesis. The present study was carried out to examine the effect of this peptide in healing of wounds in diabetic rabbits.Materials and methods: Twenty male New Zealand rabbits were used in this study. Diabetes mellitus was induced and the rabbits were randomly divided into two equal groups: control group and peptide group. A-full thickness punch biopsy was made to create a wound of about 10 mm on the right ears of all rabbits. Every day, the wound was cleaned with saline in control groups. In the peptide group, 15 mg of SHMSP was applied after cleaning. On day 15th, all animals were sacrificed, and the wounds were excised with a rim of 5 mm of normal surrounding tissue. Histo-pathological assessment of wound healing, inflammatory cell infiltration, blood vessel proliferation, and collagen deposition was performed.Results: There were no deaths among the groups. There was significant increase in wound healing, blood vessel proliferation and collagen deposition, and significant decrease in inflammatory cell infiltration in the peptide group compared to the control group.Conclusion: Topical application of SHMSP improves wound healing in diabetic rabbits.","PeriodicalId":12109,"journal":{"name":"Experimental Diabetes Research","volume":"2012 ","pages":"531961"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/531961","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30750381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 7

Transcriptional mechanisms controlling miR-375 gene expression in the pancreas. 胰腺中调控miR-375基因表达的转录机制

Experimental Diabetes Research Pub Date : 2012-01-01 Epub Date: 2012-06-20 DOI: 10.1155/2012/891216

Tali Avnit-Sagi, Tal Vana, Michael D Walker

{"title":"Transcriptional mechanisms controlling miR-375 gene expression in the pancreas.","authors":"Tali Avnit-Sagi, Tal Vana, Michael D Walker","doi":"10.1155/2012/891216","DOIUrl":"https://doi.org/10.1155/2012/891216","url":null,"abstract":"MicroRNAs (miRNAs) are a class of small non-coding RNAs that play an important role in mediating a broad and expanding range of biological activities. miR-375 is expressed selectively in the pancreas. We have previously shown that selective expression of miR-375 in pancreatic beta cells is controlled by transcriptional mechanisms operating through a TATA box-containing promoter. Expression of miR-375 has been reported in non-beta cells within the endocrine pancreas, and indeed inactivation of miR-375 leads to perturbation in cell mass and number of both alpha and beta cells. Consistent with its expression throughout the endocrine pancreas, we now show that the promoter of the miR-375 gene shows selective activity in pancreatic endocrine alpha cells, comparable to that observed in beta cells. We previously identified a novel negative regulatory element located downstream of the miR-375 gene transcription start site. By generating luciferase reporter genes, we now show that the sequence is functional also when positioned upstream of a heterologous promoter, thus proving that the repressor effect is mediated at least in part at the level of transcription. Further characterization of the transcriptional control mechanism regulating expression of miR-375 and other pancreatic miRNAs will contribute to a better understanding of pancreas development and function.","PeriodicalId":12109,"journal":{"name":"Experimental Diabetes Research","volume":"2012 ","pages":"891216"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/891216","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30750385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 17

Hyperglycemia induces the variations of 11β-hydroxysteroid dehydrogenase type 1 and peroxisome proliferator-activated receptor-γ expression in hippocampus and hypothalamus of diabetic rats. 高血糖可引起糖尿病大鼠海马和下丘脑11β-羟基类固醇脱氢酶1型和过氧化物酶体增殖物激活受体-γ表达的变化。

Experimental Diabetes Research Pub Date : 2012-01-01 Epub Date: 2012-06-26 DOI: 10.1155/2012/107130

Wen-wen Qi, Li-yong Zhong, Xiao-rong Li, Guang Li, Zhao-xia Liu, Jin-feng Hu, Nai-hong Chen

{"title":"Hyperglycemia induces the variations of 11β-hydroxysteroid dehydrogenase type 1 and peroxisome proliferator-activated receptor-γ expression in hippocampus and hypothalamus of diabetic rats.","authors":"Wen-wen Qi, Li-yong Zhong, Xiao-rong Li, Guang Li, Zhao-xia Liu, Jin-feng Hu, Nai-hong Chen","doi":"10.1155/2012/107130","DOIUrl":"https://doi.org/10.1155/2012/107130","url":null,"abstract":"In this paper, we first observed that there were differences in expressions of 11β-HSD1 and PPAR-γ, in hippocampi and hypothalami, among constant hyperglycemia group, control group and the fluctuant glycemia group, using Immunohistochemical analysis. However, whether in expression o f 11β-HSD1 or PPAR-γ, there were no statistic differences between the control group or the fluctuant glycemia group. So, we removed the fluctuant glycemia group, retaining only constant hyperglycemia group and control group, being fed for 8 weeks. After 8 weeks of induction, 11β-HSD1 expression increased and PPAR-γ expression decreased in the constant hyperglycemia group compared with control group, both in hippocampi and hypothalami, by Western Blot. The constant hyperglycemia group also showed impaired cognition in MORRIS watermaze, lower serum corticosterone level, and higher Serum ACTH concentration after 8 weeks. We inferred that the cognition impairment may be related to the abnormal expression of 11β-HSD1 and PPAR-γ in central nerves system. As for 11β-HSD1 is a regulating enzyme, converting the inactive 11-dehydrocorticosterone into the active glucocorticoid corticosterone, thus amplifying GC action in local tissues. It is also well known that high local GC levels can affect the cognitive function. In addition, PPAR-a protective receptor, which is related to cognition.","PeriodicalId":12109,"journal":{"name":"Experimental Diabetes Research","volume":"2012 ","pages":"107130"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/107130","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30760326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 18

Effects of rosiglitazone with insulin combination therapy on oxidative stress and lipid profile in left ventricular muscles of diabetic rats. 罗格列酮与胰岛素联合治疗对糖尿病大鼠左心室肌氧化应激及血脂的影响。

Experimental Diabetes Research Pub Date : 2012-01-01 Epub Date: 2012-07-05 DOI: 10.1155/2012/905683

Servet Kavak, Lokman Ayaz, Mustafa Emre

{"title":"Effects of rosiglitazone with insulin combination therapy on oxidative stress and lipid profile in left ventricular muscles of diabetic rats.","authors":"Servet Kavak, Lokman Ayaz, Mustafa Emre","doi":"10.1155/2012/905683","DOIUrl":"10.1155/2012/905683","url":null,"abstract":"Purpose: In this study, we tested the hypothesis that rosiglitazone (RSG) with insulin is able to quench oxidative stress initiated by high glucose through prevention of NAD(P)H oxidase activation.Methods and materials: Male albino Wistar rats were randomly divided into an untreated control group (C), a diabetic group (D) that was treated with a single intraperitoneal injection of streptozotocin (45 mg kg(-1)), and rosiglitazone group that was treated with RSG twice daily by gavage and insulin once daily by subcutaneous injection (group B). HbA1c and blood glucose levels in the circulation and malondialdehyde and 3-nitrotyrosine levels in left ventricular muscle were measured.Result: Treatment of D rats with group B resulted in a time-dependent decrease in blood glucose. We found that the lipid profile and HbA1c levels in group B reached the control group D rat values at the end of the treatment period. There was an increase in 3-nitrotyrosine levels in group D compared to group C. Malondialdehyde and 3-nitrotyrosine levels were found to be decreased in group B compared to group D (P < 0.05).Conclusion: Our data suggests that the treatment of diabetic rats with group B for 8 weeks may decrease the oxidative/nitrosative stress in left ventricular tissue of rats. Thus, in diabetes-related vascular diseases, group B treatment may be cardioprotective.","PeriodicalId":12109,"journal":{"name":"Experimental Diabetes Research","volume":"2012 ","pages":"905683"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/905683","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30788562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 7

The synergistic effect of valsartan and LAF237 [(S)-1-[(3-hydroxy-1-adamantyl)ammo]acetyl-2-cyanopyrrolidine] on vascular oxidative stress and inflammation in type 2 diabetic mice. 缬沙坦与LAF237 [(S)-1-[(3-羟基-1-金刚烷基)弹药]乙酰-2-氰吡啶]对2型糖尿病小鼠血管氧化应激和炎症的协同作用。

Experimental Diabetes Research Pub Date : 2012-01-01 Epub Date: 2012-03-15 DOI: 10.1155/2012/146194

Min Shen, Dongdong Sun, Weijie Li, Bing Liu, Shenxu Wang, Zheng Zhang, Feng Cao

{"title":"The synergistic effect of valsartan and LAF237 [(S)-1-[(3-hydroxy-1-adamantyl)ammo]acetyl-2-cyanopyrrolidine] on vascular oxidative stress and inflammation in type 2 diabetic mice.","authors":"Min Shen, Dongdong Sun, Weijie Li, Bing Liu, Shenxu Wang, Zheng Zhang, Feng Cao","doi":"10.1155/2012/146194","DOIUrl":"https://doi.org/10.1155/2012/146194","url":null,"abstract":"Aim: To investigate the combination effects and mechanisms of valsartan (angiotensin II type 1 receptor blocker) and LAF237 (DPP-IV inhibitor) on prevention against oxidative stress and inflammation injury in db/db mice aorta.Methods: Db/db mice (n = 40) were randomized to receive valsartan, LAF237, valsartan plus LAF237, or saline. Oxidative stress and inflammatory reaction in diabetic mice aorta were examined.Results: Valsartan or LAF237 pretreatment significantly increased plasma GLP-1 expression, reduced apoptosis of endothelial cells isolated from diabetic mice aorta. The expression of NAD(P)H oxidase subunits also significantly decreased resulting in decreased superoxide production and ICAM-1 (fold change: valsartan : 7.5 ± 0.7, P < 0.05; LAF237: 10.2 ± 1.7, P < 0.05), VCAM-1 (fold change: valsartan : 5.2 ± 1.2, P < 0.05; LAF237: 4.8 ± 0.6, P < 0.05), and MCP-1 (fold change: valsartan: 3.2 ± 0.6, LAF237: 4.7 ± 0.8; P < 0.05) expression. Moreover, the combination treatment with valsartan and LAF237 resulted in a more significant increase of GLP-1 expression. The decrease of the vascular oxidative stress and inflammation reaction was also higher than monotherapy with valsartan or LAF237.Conclusion: These data indicated that combination treatment with LAF237 and valsartan acts in a synergistic manner on vascular oxidative stress and inflammation in type 2 diabetic mice.","PeriodicalId":12109,"journal":{"name":"Experimental Diabetes Research","volume":"2012 ","pages":"146194"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/146194","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30549909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 11

L(+) and D(-) lactate are increased in plasma and urine samples of type 2 diabetes as measured by a simultaneous quantification of L(+) and D(-) lactate by reversed-phase liquid chromatography tandem mass spectrometry. 通过反相液相色谱串联质谱同时定量L(+)和D(-)乳酸测定，2型糖尿病患者血浆和尿液样品中的L(+)和D(-)乳酸增加。

Experimental Diabetes Research Pub Date : 2012-01-01 Epub Date: 2012-03-08 DOI: 10.1155/2012/234812

Jean L J M Scheijen, Nordin M J Hanssen, Marjo P H van de Waarenburg, Daisy M A E Jonkers, Coen D A Stehouwer, Casper G Schalkwijk

{"title":"L(+) and D(-) lactate are increased in plasma and urine samples of type 2 diabetes as measured by a simultaneous quantification of L(+) and D(-) lactate by reversed-phase liquid chromatography tandem mass spectrometry.","authors":"Jean L J M Scheijen, Nordin M J Hanssen, Marjo P H van de Waarenburg, Daisy M A E Jonkers, Coen D A Stehouwer, Casper G Schalkwijk","doi":"10.1155/2012/234812","DOIUrl":"https://doi.org/10.1155/2012/234812","url":null,"abstract":"Background: Plasma and urinary levels of D-lactate have been linked to the presence of diabetes. Previously developed techniques have shown several limitations to further evaluate D-lactate as a biomarker for this condition.Methods: D- and L-lactate were quantified using ultraperformance liquid chromatography tandem mass spectrometry with labelled internal standard. Samples were derivatized with diacetyl-L-tartaric anhydride and separated on a C(18)-reversed phase column. D- and L-lactate were analysed in plasma and urine of controls, patients with inflammatory bowel disease (IBD), and patients with type 2 diabetes (T2DM).Results: Quantitative analysis of D- and L-lactate was achieved successfully. Calibration curves were linear (r(2) > 0.99) over the physiological and pathophysiological ranges. Recoveries for urine and plasma were between 96% and 113%. Inter- and intra-assay variations were between 2% and 9%. The limits of detection of D-lactate and L-lactate in plasma were 0.7 μmol/L and 0.2 μmol/L, respectively. The limits of detection of D-lactate and L-lactate in urine were 8.1 nmol/mmol creatinine and 4.4 nmol/mmol creatinine, respectively. Plasma and urinary levels of D- and L-lactate were increased in patients with IBD and T2DM as compared with controls.Conclusion: The presented method proved to be suitable for the quantification of D- and L-lactate and opens the possibility to explore the use of D-lactate as a biomarker.","PeriodicalId":12109,"journal":{"name":"Experimental Diabetes Research","volume":"2012 ","pages":"234812"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/234812","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30549912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 71

The effects of green tea consumption on cardiometabolic alterations induced by experimental diabetes. 绿茶对实验性糖尿病引起的心脏代谢改变的影响。

Experimental Diabetes Research Pub Date : 2012-01-01 Epub Date: 2012-02-29 DOI: 10.1155/2012/309231

Patricia Fiorino, Fabiana Sant'Anna Evangelista, Fernando Santos, Fátima Maria Motter Magri, Jan Carlo Morais O B Delorenzi, Milton Ginoza, Vera Farah

{"title":"The effects of green tea consumption on cardiometabolic alterations induced by experimental diabetes.","authors":"Patricia Fiorino, Fabiana Sant'Anna Evangelista, Fernando Santos, Fátima Maria Motter Magri, Jan Carlo Morais O B Delorenzi, Milton Ginoza, Vera Farah","doi":"10.1155/2012/309231","DOIUrl":"https://doi.org/10.1155/2012/309231","url":null,"abstract":"We evaluated cardiac autonomic modulation by heart rate (HRV), and arterial pressure variability (APV), and metabolic response in streptozotocin diabetic rats treated with green tea. Male Wistar rats were separated in groups: control, drinking tap water (C), green tea-treated (GT) group, diabetic, drinking tap water (D), and diabetic, treated with green tea (DGT). Kidney mass was greater in D and DGT than in C and GT, but reduced in DGT compared to D. Green tea prevented the increase in creatinine clearance and reduced hyperglycemia in DGT compared to D. Arterial pressure was increased in GT and decreased in D compared to C. HRV was reduced in D compared with all groups. APV was decreased in D compared to C and recovery in DGT. Sympathetic modulation of APV was decreased in D compared with all groups. Green tea reduced hyperglycemia, prevented renal injury and autonomic dysfunction, suggesting reduced cardiovascular risk and target organ damage in diabetes.","PeriodicalId":12109,"journal":{"name":"Experimental Diabetes Research","volume":"2012 ","pages":"309231"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/309231","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30549914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 18

TXNIP links innate host defense mechanisms to oxidative stress and inflammation in retinal Muller glia under chronic hyperglycemia: implications for diabetic retinopathy. TXNIP将先天宿主防御机制与慢性高血糖下视网膜Muller胶质细胞的氧化应激和炎症联系起来:对糖尿病视网膜病变的影响。

Experimental Diabetes Research Pub Date : 2012-01-01 Epub Date: 2012-03-18 DOI: 10.1155/2012/438238

Takhellambam S Devi, Icksoo Lee, Maik Hüttemann, Ashok Kumar, Kwaku D Nantwi, Lalit P Singh

{"title":"TXNIP links innate host defense mechanisms to oxidative stress and inflammation in retinal Muller glia under chronic hyperglycemia: implications for diabetic retinopathy.","authors":"Takhellambam S Devi, Icksoo Lee, Maik Hüttemann, Ashok Kumar, Kwaku D Nantwi, Lalit P Singh","doi":"10.1155/2012/438238","DOIUrl":"https://doi.org/10.1155/2012/438238","url":null,"abstract":"Thioredoxin Interacting Protein (TXNIP) mediates retinal inflammation, gliosis, and apoptosis in experimental diabetes. Here, we investigate the temporal response of Muller glia to high glucose (HG) and TXNIP expression using a rat Muller cell line (rMC1) in culture. We examined if HG-induced TXNIP expression evokes host defense mechanisms in rMC1 in response to metabolic abnormalities. HG causes sustained up-regulation of TXNIP (2 h to 5 days), ROS generation, ATP depletion, ER stress, and inflammation. Various cellular defense mechanisms are activated by HG: (i) NLRP3 inflammasome, (ii) ER stress response (sXBP1), (iii) hypoxic-like HIF-1α induction, (iv) autophagy/mitophagy, and (v) apoptosis. We also found in vivo that streptozocin-induced diabetic rats have higher retinal TXNIP and innate immune response gene expression than normal rats. Knock down of TXNIP by intravitreal siRNA reduces inflammation (IL-1β) and gliosis (GFAP) in the diabetic retina. TXNIP ablation in vitro prevents ROS generation, restores ATP level and autophagic LC3B induction in rMC1. Thus, our results show that HG sustains TXNIP up-regulation in Muller glia and evokes a program of cellular defense/survival mechanisms that ultimately lead to oxidative stress, ER stress/inflammation, autophagy and apoptosis. TXNIP is a potential target to ameliorate blinding ocular complications of diabetic retinopathy.","PeriodicalId":12109,"journal":{"name":"Experimental Diabetes Research","volume":"2012 ","pages":"438238"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/438238","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30549915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 181