Experimental Diabetes Research最新文献_第6页

Ca+2/calmodulin-dependent protein kinase mediates glucose toxicity-induced cardiomyocyte contractile dysfunction. Ca+2/钙调素依赖性蛋白激酶介导葡萄糖毒性诱导的心肌细胞收缩功能障碍。

Experimental Diabetes Research Pub Date : 2012-01-01 Epub Date: 2012-06-18 DOI: 10.1155/2012/829758

Rong-Huai Zhang, Haitao Guo, Machender R Kandadi, Xiao-Ming Wang, Jun Ren

{"title":"Ca+2/calmodulin-dependent protein kinase mediates glucose toxicity-induced cardiomyocyte contractile dysfunction.","authors":"Rong-Huai Zhang, Haitao Guo, Machender R Kandadi, Xiao-Ming Wang, Jun Ren","doi":"10.1155/2012/829758","DOIUrl":"https://doi.org/10.1155/2012/829758","url":null,"abstract":"(1) Hyperglycemia leads to cytotoxicity in the heart. Although several theories are postulated for glucose toxicity-induced cardiomyocyte dysfunction, the precise mechanism still remains unclear. (2) This study was designed to evaluate the impact of elevated extracellular Ca(2+) on glucose toxicity-induced cardiac contractile and intracellular Ca(2+) anomalies as well as the mechanism(s) involved with a focus on Ca(2+)/calmodulin (CaM)-dependent kinase. Isolated adult rat cardiomyocytes were maintained in normal (NG, 5.5 mM) or high glucose (HG, 25.5 mM) media for 6-12 hours. Contractile indices were measured including peak shortening (PS), maximal velocity of shortening/relengthening (±dL/dt), time-to-PS (TPS), and time-to-90% relengthening (TR(90)). (3) Cardiomyocytes maintained with HG displayed abnormal mechanical function including reduced PS, ±dL/dt, and prolonged TPS, TR(90) and intracellular Ca(2+) clearance. Expression of intracellular Ca(2+) regulatory proteins including SERCA2a, phospholamban and Na(+)-Ca(2+) exchanger were unaffected whereas SERCA activity was inhibited by HG. Interestingly, the HG-induced mechanical anomalies were abolished by elevated extracellular Ca(2+) (from 1.0 to 2.7 mM). Interestingly, the high extracellular Ca(2+)-induced beneficial effect against HG was abolished by the CaM kinase inhibitor KN93. (4) These data suggest that elevated extracellular Ca(2+) protects against glucose toxicity-induced cardiomyocyte contractile defects through a mechanism associated with CaM kinase.","PeriodicalId":12109,"journal":{"name":"Experimental Diabetes Research","volume":"2012 ","pages":"829758"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/829758","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30728107","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: 6

Obesity and appetite control. 肥胖症与食欲控制

Experimental Diabetes Research Pub Date : 2012-01-01 Epub Date: 2012-08-01 DOI: 10.1155/2012/824305

Keisuke Suzuki, Channa N Jayasena, Stephen R Bloom

引用次数: 0

Effects of glucagon-like peptide-1 receptor agonists on body weight: a meta-analysis. 胰高血糖素样肽-1受体激动剂对体重的影响:一项meta分析。

Experimental Diabetes Research Pub Date : 2012-01-01 Epub Date: 2012-05-20 DOI: 10.1155/2012/672658

Matteo Monami, Ilaria Dicembrini, Niccolò Marchionni, Carlo M Rotella, Edoardo Mannucci

{"title":"Effects of glucagon-like peptide-1 receptor agonists on body weight: a meta-analysis.","authors":"Matteo Monami, Ilaria Dicembrini, Niccolò Marchionni, Carlo M Rotella, Edoardo Mannucci","doi":"10.1155/2012/672658","DOIUrl":"https://doi.org/10.1155/2012/672658","url":null,"abstract":"Glucagon-Like Peptide-1 receptor agonists (GLP-1RAs), approved as glucose-lowering drugs for the treatment of type 2 diabetes, have also been shown to reduce body weight. An extensive Medline, Cochrane database, and Embase search for \"exenatide,\" \"liraglutide,\" \"albiglutide,\" \"semaglutide,\" and \"lixisenatide\" was performed, collecting all randomized clinical trials on humans up to December 15, 2011, with a duration of at least 24 weeks, comparing GLP-1 receptor agonists with either placebo or active drugs. Twenty two (7,859 patients) and 7 (2,416 patients) trials with available results on body weight at 6 and 12 months, respectively, were included. When compared with placebo, GLP-1RAs determine a reduction of BMI at 6 months of -1.0 [-1.3; -0.6] kg/m(2). Considering the average BMI at baseline (32.4 kg/m(2)) these data means a weight reduction of about 3% at 6 months. This result could seem modest from a clinical standpoint; however, it could be affected by many factors contributing to an underestimation of the effect of GLP-1RA on body weight, such as non adequate doses, inclusion criteria, efficacy of GLP-1RA on reducing glycosuria, and association to non-pharmacological interventions not specifically aimed to weight reduction.","PeriodicalId":12109,"journal":{"name":"Experimental Diabetes Research","volume":"2012 ","pages":"672658"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/672658","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30674114","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: 97

Oxytocin and psychological factors affecting type 2 diabetes mellitus. 催产素与影响2型糖尿病的心理因素。

Experimental Diabetes Research Pub Date : 2012-01-01 Epub Date: 2012-09-10 DOI: 10.1155/2012/560864

K Kontoangelos, A E Raptis, C C Papageorgiou, P C Tsiotra, G N Papadimitriou, A D Rabavilas, G Dimitriadis, S A Raptis

{"title":"Oxytocin and psychological factors affecting type 2 diabetes mellitus.","authors":"K Kontoangelos, A E Raptis, C C Papageorgiou, P C Tsiotra, G N Papadimitriou, A D Rabavilas, G Dimitriadis, S A Raptis","doi":"10.1155/2012/560864","DOIUrl":"https://doi.org/10.1155/2012/560864","url":null,"abstract":"Background: The aim of this study was to investigate the association of oxytocin with trait and state psychological factors in type 2 diabetic patients.Methods: OXT and psychological variables were analyzed from 86 controlled diabetic patients (glycosylated haemoglobin A1c (HbA1c) < 7%) from 45 uncontrolled diabetic patients (HbA1c ≥ 7). Psychological characteristics were assessed with the Eysenck Personality Questionnaire (EPQ), while state psychological characteristics were measured with the Symptom Checklist 90-R (SCL 90-R). Blood samples were taken for measuring oxytocin in both subgroups during the initial phase of the study. One year later, the uncontrolled diabetic patients were reevaluated with the use of the same psychometric instruments.Results: During the first evaluation of the uncontrolled diabetic patients, a statistically significant positive relationship between the levels of OXT and psychoticism in EPQ rating scale (P < 0.013) was observed. For controlled diabetic patients, a statistically significant negative relationship between oxytocin and somatization (P < 0.030), as well as obsessive-compulsive scores (P < 0.047) in SCL-90 rating scale, was observed. During the second assessment, the values of OXT decreased when the patients managed to control their metabolic profile.Conclusions: The OXT is in association with psychoticism, somatization, and obsessionality may be implicated in T2DM.","PeriodicalId":12109,"journal":{"name":"Experimental Diabetes Research","volume":"2012 ","pages":"560864"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/560864","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30921939","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: 10

Cardiovascular disease risk in the offspring of diabetic women: the impact of the intrauterine environment. 糖尿病妇女子代心血管疾病风险:宫内环境的影响

Experimental Diabetes Research Pub Date : 2012-01-01 Epub Date: 2012-10-22 DOI: 10.1155/2012/565160

Laura J Marco, Kate McCloskey, Peter J Vuillermin, David Burgner, Joanne Said, Anne-Louise Ponsonby

引用次数: 57

The biological behaviors of rat dermal fibroblasts can be inhibited by high levels of MMP9. 高水平的MMP9可抑制大鼠真皮成纤维细胞的生物学行为。

Experimental Diabetes Research Pub Date : 2012-01-01 Epub Date: 2012-04-22 DOI: 10.1155/2012/494579

Sheng-Neng Xue, Juan Lei, Chuan Yang, Diao-Zhu Lin, Li Yan

{"title":"The biological behaviors of rat dermal fibroblasts can be inhibited by high levels of MMP9.","authors":"Sheng-Neng Xue, Juan Lei, Chuan Yang, Diao-Zhu Lin, Li Yan","doi":"10.1155/2012/494579","DOIUrl":"https://doi.org/10.1155/2012/494579","url":null,"abstract":"Aims: To explore the effects of the high expression of MMP9 on biological behaviors of fibroblasts.Methods: High glucose and hyperhomocysteine were used to induce MMP9 expression in skin fibroblasts. Cell proliferation was detected by flow cytometry and cell viability by CCK-8. ELISA assay was used to detect collagen (hydroxyproline) secretion. Scratch test was employed to evaluate horizontal migration of cells and transwell method to evaluate vertical migration of cells.Results: The mRNA and protein expressions of MMP9 and its protease activity were significantly higher in cells treated with high glucose and hyperhomocysteine than those in control group. At the same time, the S-phase cell ratio, proliferation index, cell viability, collagen (hydroxyproline) secretion, horizontal migration rate, and the number of vertical migration cells decreased in high-glucose and hyperhomocysteine-treated group. Tissue inhibitor of metalloproteinase 1 (TIMP1), which inhibits the activity of MMP9, recovered the above biological behaviors.Conclusions: High expression of MMP9 in skin fibroblasts could be induced by cultureing in high glucose and hyperhomocysteine medium, which inhibited cell biological behaviors. Inhibitions could be reversed by TIMP1. The findings suggested that MMP9 deters the healing of diabetic foot ulcers by inhibiting the biological behaviors of fibroblasts.","PeriodicalId":12109,"journal":{"name":"Experimental Diabetes Research","volume":"2012 ","pages":"494579"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/494579","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30610804","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: 27

The antioxidant 3H-1,2-dithiole-3-thione potentiates advanced glycation end-product-induced oxidative stress in SH-SY5Y cells. 抗氧化剂3h -1,2-二硫基-3-硫酮增强SH-SY5Y细胞中晚期糖基化终产物诱导的氧化应激。

Experimental Diabetes Research Pub Date : 2012-01-01 Epub Date: 2012-05-17 DOI: 10.1155/2012/137607

Robert Pazdro, John R Burgess

{"title":"The antioxidant 3H-1,2-dithiole-3-thione potentiates advanced glycation end-product-induced oxidative stress in SH-SY5Y cells.","authors":"Robert Pazdro, John R Burgess","doi":"10.1155/2012/137607","DOIUrl":"https://doi.org/10.1155/2012/137607","url":null,"abstract":"Oxidative stress is implicated as a major factor in the development of diabetes complications and is caused in part by advanced glycation end products (AGEs). AGEs ligate to the receptor for AGEs (RAGE), promoting protein kinase C (PKC)-dependent activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and superoxide radical generation. While scavenging antioxidants are protective against AGEs, it is unknown if induction of endogenous antioxidant defenses has the same effect. In this study, we confirmed that the compound 3H-1,2-dithiole-3-thione (D3T) increases reduced-state glutathione (GSH) concentrations and NADPH:quinone oxidoreductase 1 (NQO1) activity in SH-SY5Y cells and provides protection against H(2)O(2). Surprisingly, D3T potentiated oxidative damage caused by AGEs. In comparison to vehicle controls, D3T caused greater AGE-induced cytotoxicity and depletion of intracellular GSH levels while offering no protection against neurite degeneration or protein carbonylation. D3T potentiated AGE-induced reactive oxygen species (ROS) formation, an effect abrogated by inhibitors of PKC and NADPH oxidase. This study suggests that chemical induction of endogenous antioxidant defenses requires further examination in models of diabetes.","PeriodicalId":12109,"journal":{"name":"Experimental Diabetes Research","volume":"2012 ","pages":"137607"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/137607","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30674112","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: 25

Hepatic mitochondrial alterations and increased oxidative stress in nutritional diabetes-prone Psammomys obesus model. 营养性糖尿病易感性肥胖模型肝脏线粒体改变和氧化应激增加

Experimental Diabetes Research Pub Date : 2012-01-01 Epub Date: 2012-05-17 DOI: 10.1155/2012/430176

Saida Bouderba, M Nieves Sanz, Carlos Sánchez-Martín, M Yehia El-Mir, Gloria R Villanueva, Dominique Detaille, E Ahmed Koceïr

{"title":"Hepatic mitochondrial alterations and increased oxidative stress in nutritional diabetes-prone Psammomys obesus model.","authors":"Saida Bouderba, M Nieves Sanz, Carlos Sánchez-Martín, M Yehia El-Mir, Gloria R Villanueva, Dominique Detaille, E Ahmed Koceïr","doi":"10.1155/2012/430176","DOIUrl":"https://doi.org/10.1155/2012/430176","url":null,"abstract":"Mitochondrial dysfunction is considered to be a pivotal component of insulin resistance and associated metabolic diseases. Psammomys obesus is a relevant model of nutritional diabetes since these adult animals exhibit a state of insulin resistance when fed a standard laboratory chow, hypercaloric for them as compared to their natural food. In this context, alterations in bioenergetics were studied. Using liver mitochondria isolated from these rats fed such a diet for 18 weeks, oxygen consumption rates, activities of respiratory complexes, and content in cytochromes were examined. Levels of malondialdehyde (MDA) and gluthatione (GSH) were measured in tissue homogenates. Diabetic Psammomys showed a serious liver deterioration (hepatic mass accretion, lipids accumulation), accompanied by an enhanced oxidative stress (MDA increased, GSH depleted). On the other hand, both ADP-dependent and uncoupled respirations greatly diminished below control values, and the respiratory flux to cytochrome oxydase was mildly lowered. Furthermore, an inhibition of complexes I and III together with an activation of complex II were found. With emergence of oxidative stress, possibly related to a defect in oxidative phosphorylation, some molecular adjustments could contribute to alleviate, at least in part, the deleterious outcomes of insulin resistance in this gerbil species.","PeriodicalId":12109,"journal":{"name":"Experimental Diabetes Research","volume":"2012 ","pages":"430176"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/430176","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30674113","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: 31

Single diabetic QTL derived from OLETF rat is a sufficient agent for severe diabetic phenotype in combination with leptin-signaling deficiency. 来源于 OLETF 大鼠的单个糖尿病 QTL 是导致严重糖尿病表型和瘦素信号缺乏症的充分因素。

Experimental Diabetes Research Pub Date : 2012-01-01 Epub Date: 2012-12-05 DOI: 10.1155/2012/858121

Hiroyuki Kose, Takahisa Yamada, Kozo Matsumoto

{"title":"Single diabetic QTL derived from OLETF rat is a sufficient agent for severe diabetic phenotype in combination with leptin-signaling deficiency.","authors":"Hiroyuki Kose, Takahisa Yamada, Kozo Matsumoto","doi":"10.1155/2012/858121","DOIUrl":"10.1155/2012/858121","url":null,"abstract":"Obesity has been considered one of the leading causative agents for diseases such as type 2 diabetes, stroke, and heart attack. Due to their complex etiology, establishing a useful animal model is increasingly crucial for better molecular understanding of how obesity influences on disease development. OLETF rat is a spontaneous model of type 2 diabetes. We mapped 14 hyperglycemia QTLs in the genome of the OLETF rat and subsequently generated a panel of congenic strains each possessing OB-R mutation in F344 genetic background. Here we show that one of the loci, Nidd2/of, is highly responsive to obesity. When leptin receptor mutation is introgressed into the Nidd2/of congenic strain, the rat showed hyperglycemia equivalent to that of the parental OLETF rat. This suggests that the Nidd2/of locus has a strong genetic interaction with leptin signaling pathway. Furthermore, when another hyperglycemia QTL Nidd1/of is additionally combined, the strain developed overt diabetes. A single QTL dissected out in spontaneous model normally exerts only mild effect on the quantitative trait, which makes it difficult to clone the gene. Our new model may help not only to identify the causative gene but also to investigate how obesity interacts with a QTL to regulate diabetic traits.","PeriodicalId":12109,"journal":{"name":"Experimental Diabetes Research","volume":"2012 ","pages":"858121"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3529458/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31147460","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: 0

MicroRNAs in insulin resistance and obesity. 胰岛素抵抗和肥胖中的microrna。

Experimental Diabetes Research Pub Date : 2012-01-01 Epub Date: 2012-07-18 DOI: 10.1155/2012/484696

Michael D Williams, Geraldine M Mitchell

引用次数: 134