Experimental Diabetes Research最新文献

{"title":"Emerging pharmacotherapies for diabetic macular edema.","authors":"Golnaz Javey,&nbsp;Stephen G Schwartz,&nbsp;Harry W Flynn","doi":"10.1155/2012/548732","DOIUrl":"https://doi.org/10.1155/2012/548732","url":null,"abstract":"<p><p>Diabetic macular edema (DME) remains an important cause of visual loss in patients with diabetes mellitus. Although photocoagulation and intensive control of systemic metabolic factors have been reported to achieve improved outcomes in large randomized clinical trials (RCTs), some patients with DME continue to lose vision despite treatment. Pharmacotherapies for DME include locally and systemically administered agents. We review several agents that have been studied for the treatment of DME.</p>","PeriodicalId":12109,"journal":{"name":"Experimental Diabetes Research","volume":"2012 ","pages":"548732"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/548732","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30551526","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}

{"title":"Regulation of LYRM1 gene expression by free fatty acids, adipokines, and rosiglitazone in 3T3-L1 adipocytes.","authors":"Min Zhang,&nbsp;Hai-Ming Zhao,&nbsp;Zhen-Ying Qin,&nbsp;Rui Qin,&nbsp;Xiao-Hui Chen,&nbsp;Ya-Ping Zhao,&nbsp;Chun-Mei Zhang,&nbsp;Chun-Lin Gao,&nbsp;Chun Zhu,&nbsp;Chen-Bo Ji,&nbsp;Xin-Guo Cao,&nbsp;Xi-Rong Guo","doi":"10.1155/2012/820989","DOIUrl":"https://doi.org/10.1155/2012/820989","url":null,"abstract":"<p><p>LYR motif containing 1 (LYRM1) is a novel gene that is abundantly expressed in the adipose tissue of obese subjects and is involved in insulin resistance. In this study, free fatty acids (FFAs) and tumor necrosis factor-α (TNF-α) are shown to upregulate LYRM1 mRNA expression in 3T3-L1 adipocytes. Conversely, resistin and rosiglitazone exert an inhibitory effect on LYRM1 mRNA expression. These results suggest that the expression of LYRM1 mRNA is affected by a variety of factors that are related to insulin sensitivity. LYRM1 may be an important mediator in the development of obesity-related insulin resistance.</p>","PeriodicalId":12109,"journal":{"name":"Experimental Diabetes Research","volume":"2012 ","pages":"820989"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/820989","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30132351","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}

{"title":"Common variants of homocysteine metabolism pathway genes and risk of type 2 diabetes and related traits in Indians.","authors":"Ganesh Chauhan,&nbsp;Ismeet Kaur,&nbsp;Rubina Tabassum,&nbsp;Om Prakash Dwivedi,&nbsp;Saurabh Ghosh,&nbsp;Nikhil Tandon,&nbsp;Dwaipayan Bharadwaj","doi":"10.1155/2012/960318","DOIUrl":"https://doi.org/10.1155/2012/960318","url":null,"abstract":"<p><p>Hyperhomocysteinemia, a risk factor for cardiovascular disorder, obesity, and type 2 diabetes, is prevalent among Indians who are at high risk of these metabolic disorders. We evaluated association of common variants of genes involved in homocysteine metabolism or its levels with type 2 diabetes, obesity, and related traits in North Indians. We genotyped 90 variants in initial phase (2.115 subjects) and replicated top signals in an independent sample set (2.085 subjects). The variant MTHFR-rs1801133 was the top signal for association with type 2 diabetes (OR = 0.78 (95%  CI = 0.67-0.92), P = 0.003) and was also associated with 2 h postload plasma glucose (P = 0.04), high-density lipoprotein cholesterol (P = 0.004), and total cholesterol (P = 0.01) in control subjects. These associations were neither replicated nor significant after meta-analysis. Studies involving a larger study population and different ethnic groups are required before ruling out the role of these important candidate genes in type 2 diabetes, obesity, and related traits.</p>","PeriodicalId":12109,"journal":{"name":"Experimental Diabetes Research","volume":"2012 ","pages":"960318"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/960318","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30176072","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}

{"title":"Circulating TGF-β1, glycation, and oxidation in children with diabetes mellitus type 1.","authors":"Vladimír Jakuš,&nbsp;Michal Sapák,&nbsp;Jana Kostolanská","doi":"10.1155/2012/510902","DOIUrl":"https://doi.org/10.1155/2012/510902","url":null,"abstract":"<p><p>The present study investigates the relationship between diabetes metabolic control represented by levels of HbA1c, early glycation products-(fructosamine (FAM)), serum-advanced glycation end products (s-AGEs), lipoperoxidation products (LPO), advanced oxidation protein products (AOPP) and circulating TGF-β in young patients with DM1. The study group consisted of 79 patients with DM1 (8-18 years). 31 healthy children were used as control (1-16 years). Baseline characteristics of patients were compared by Student's t-test and nonparametric Mann-Whitney test (Statdirect), respectively. The correlations between the measured parameters were examined using Pearson correlation coefficient r and Spearman's rank test, respectively. A P value < 0.05 was considered as statistically significant. HbA1c was measured by LPLC, s-AGEs spectrofluorimetrically, LPO and AOPP spectrophotometrically and TGF-β by ELISA. Our results showed that parameters of glycation and oxidation are significantly higher in patients with DM1 than in healthy control. The level of serum TGF-β was significantly higher in diabetics in comparison with control: 7.1(3.6; 12.6) versus 1.6(0.8; 3.9) ng/mL. TGF-β significantly correlated with age and duration of DM1. There was not found any significant relation between TGF-β and parameres of glycation and oxidation. However, these results do not exclude the association between TGF-β and the onset of diabetic complications.</p>","PeriodicalId":12109,"journal":{"name":"Experimental Diabetes Research","volume":"2012 ","pages":"510902"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/510902","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30964114","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}

{"title":"Effects of restricted fructose access on body weight and blood pressure circadian rhythms.","authors":"Danielle Senador,&nbsp;Swapnil Shewale,&nbsp;Maria Claudia Irigoyen,&nbsp;Khalid M Elased,&nbsp;Mariana Morris","doi":"10.1155/2012/459087","DOIUrl":"https://doi.org/10.1155/2012/459087","url":null,"abstract":"High-fructose diet is known to produce cardiovascular and metabolic pathologies. The objective was to determine whether the timing of high fructose (10% liquid solution) intake affect the metabolic and cardiovascular outcomes. Male C57BL mice with radiotelemetric probes were divided into four groups: (1) 24 h water (control); (2) 24 h fructose (F24); (3) 12 h fructose during the light phase (F12L); (4) 12 h fructose during the dark phase (F12D). All fructose groups had higher fluid intake. Body weight was increased in mice on restricted access with no difference in total caloric intake. Fasting glycemia was higher in groups with restricted access. F24 mice showed a fructose-induced blood pressure increase during the dark period. Blood pressure circadian rhythms were absent in F12L mice. Results suggest that the timing of fructose intake is an important variable in the etiology of cardiovascular and metabolic pathologies produced by high fructose consumption.","PeriodicalId":12109,"journal":{"name":"Experimental Diabetes Research","volume":" ","pages":"459087"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/459087","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40184569","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}

{"title":"It is all in the blood: the multifaceted contribution of circulating progenitor cells in diabetic complications.","authors":"Gian Paolo Fadini, Angelo Avogaro","doi":"10.1155/2012/742976","DOIUrl":"10.1155/2012/742976","url":null,"abstract":"<p><p>Diabetes mellitus (DM) is a worldwide growing disease and represents a huge social and healthcare problem owing to the burden of its complications. Micro- and macrovascular diabetic complications arise from excess damage through well-known biochemical pathways. Interestingly, microangiopathy hits the bone marrow (BM) microenvironment with features similar to retinopathy, nephropathy and neuropathy. The BM represents a reservoir of progenitor cells for multiple lineages, not limited to the hematopoietic system and including endothelial cells, smooth muscle cells, cardiomyocytes, and osteogenic cells. All these multiple progenitor cell lineages are profoundly altered in the setting of diabetes in humans and animal models. Reduction of endothelial progenitor cells (EPCs) along with excess smooth muscle progenitor (SMP) and osteoprogenitor cells creates an imbalance that promote the development of micro- and macroangiopathy. Finally, an excess generation of BM-derived fusogenic cells has been found to contribute to diabetic complications in animal models. Taken together, a growing amount of literature attributes to circulating progenitor cells a multi-faceted role in the pathophysiology of DM, setting a novel scenario that puts BM and the blood at the centre of the stage.</p>","PeriodicalId":12109,"journal":{"name":"Experimental Diabetes Research","volume":" ","pages":"742976"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3324138/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40196353","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}

{"title":"Guards and culprits in the endoplasmic reticulum: glucolipotoxicity and β-cell failure in type II diabetes.","authors":"Udayakumar Karunakaran,&nbsp;Han-Jong Kim,&nbsp;Joon-Young Kim,&nbsp;In-Kyu Lee","doi":"10.1155/2012/639762","DOIUrl":"https://doi.org/10.1155/2012/639762","url":null,"abstract":"<p><p>The endoplasmic reticulum (ER) is a cellular organelle responsible for multiple important cellular functions including the biosynthesis and folding of newly synthesized proteins destined for secretion, such as insulin. The ER participates in all branches of metabolism, linking nutrient sensing to cellular signaling. Many pathological and physiological factors perturb ER function and induce ER stress. ER stress triggers an adaptive signaling cascade, called the unfolded protein response (UPR), to relieve the stress. The failure of the UPR to resolve ER stress leads to pathological conditions such as β-cell dysfunction and death, and type II diabetes. However, much less is known about the fine details of the control and regulation of the ER response to hyperglycemia (glucotoxicity), hyperlipidemia (lipotoxicity), and the combination of both (glucolipotoxicity). This paper considers recent insights into how the response is regulated, which may provide clues into the mechanism of ER stress-mediated β-cell dysfunction and death during the progression of glucolipotoxicity-induced type II diabetes.</p>","PeriodicalId":12109,"journal":{"name":"Experimental Diabetes Research","volume":"2012 ","pages":"639762"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/639762","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30190264","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}

{"title":"Oxidative metabolism genes are not responsive to oxidative stress in rodent Beta cell lines.","authors":"Faer Morrison,&nbsp;Karen Johnstone,&nbsp;Anna Murray,&nbsp;Jonathan Locke,&nbsp;Lorna W Harries","doi":"10.1155/2012/793783","DOIUrl":"https://doi.org/10.1155/2012/793783","url":null,"abstract":"<p><p>Altered expression of oxidative metabolism genes has been described in the skeletal muscle of individuals with type 2 diabetes. Pancreatic beta cells contain low levels of antioxidant enzymes and are particularly susceptible to oxidative stress. In this study, we explored the effect of hyperglycemia-induced oxidative stress on a panel of oxidative metabolism genes in a rodent beta cell line. We exposed INS-1 rodent beta cells to low (5.6 mmol/L), ambient (11 mmol/L), and high (28 mmol/L) glucose conditions for 48 hours. Increases in oxidative stress were measured using the fluorescent probe dihydrorhodamine 123. We then measured the expression levels of a panel of 90 oxidative metabolism genes by real-time PCR. Elevated reactive oxygen species (ROS) production was evident in INS-1 cells after 48 hours (P < 0.05). TLDA analysis revealed a significant (P < 0.05) upregulation of 16 of the 90 genes under hyperglycemic conditions, although these expression differences did not reflect differences in ROS. We conclude that although altered glycemia may influence the expression of some oxidative metabolism genes, this effect is probably not mediated by increased ROS production. The alterations to the expression of oxidative metabolism genes previously observed in human diabetic skeletal muscle do not appear to be mirrored in rodent pancreatic beta cells.</p>","PeriodicalId":12109,"journal":{"name":"Experimental Diabetes Research","volume":"2012 ","pages":"793783"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/793783","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30535261","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}

{"title":"Inhibition of protein tyrosine phosphatase improves angiogenesis via enhancing Ang-1/Tie-2 signaling in diabetes.","authors":"Jian-Xiong Chen,&nbsp;Qinhui Tuo,&nbsp;Duan-Fang Liao,&nbsp;Heng Zeng","doi":"10.1155/2012/836759","DOIUrl":"https://doi.org/10.1155/2012/836759","url":null,"abstract":"<p><p>Diabetes is associated with impairment of angiogenesis such as reduction of myocardial capillary formation. Our previous studies demonstrate that disruption of Angiopoietin-1 (Ang-1)/Tie-2 signaling pathway contributes to the diabetes-associated impairment of angiogenesis. Protein tyrosine phosphatase (PTP) has a critical role in the regulation of insulin signal by inhibition of tyrosine kinase phosphorylation. In present study, we examined the role of protein tyrosine phosphatase-1 (SHP-1) in diabetes-associated impairment of Ang-1/Tie-2 angiogenic signaling and angiogenesis. SHP-1 expression was significantly increased in diabetic db/db mouse hearts. Furthermore, SHP-1 bond to Tie-2 receptor and stimulation with Ang-1 led to SHP-1 dissociation from Tie-2 in mouse heart microvascular endothelial cell (MHMEC). Exposure of MHMEC to high glucose (HG, 30 mmol/L) increased SHP-1/Tie-2 association accompanied by a significant reduction of Tie-2 phosphorylation. Exposure of MHMEC to HG also blunted Ang-1-mediated SHP-1/Tie-2 dissociation. Knockdown of SHP-1 significantly attenuated HG-induced caspase-3 activation and apoptosis in MHMEC. Treatment with PTP inhibitors restored Ang-1-induced Akt/eNOS phosphorylation and angiogenesis. Our data implicate a critical role of SHP-1 in diabetes-associated vascular complications, and that upregulation of Ang-1/Tie-2 signaling by targeting SHP-1 should be considered as a new therapeutic strategy for the treatment of diabetes-associated impairment of angiogenesis.</p>","PeriodicalId":12109,"journal":{"name":"Experimental Diabetes Research","volume":"2012 ","pages":"836759"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/836759","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30535262","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}

{"title":"Experimental models of type-2 diabetic nephropathy.","authors":"Yasuhiko Tomino,&nbsp;Mark E Cooper,&nbsp;Theodore W Kurtz,&nbsp;Yoshio Shimizu","doi":"10.1155/2012/218917","DOIUrl":"https://doi.org/10.1155/2012/218917","url":null,"abstract":"Type 2 diabetic nephropathy is one of the major long-term microvascular complications occurring in nearly 40% of diabetic patients and also a major cause of end-stage kidney disease (ESKD) throughout the world. It is assumed that the number of type 2 diabetes and diabetic nephropathy patients is increasing and that more and more patients will experience progressive renal disease due to lack of effective treatments. The pathogenesis of type 2 diabetic nephropathy includes genetic, metabolic (hyperglycemic), and/or hemodynamic factors such as glomerular hypertension and associated renal hypertrophy. There are many progressive factors in patients with type 2 diabetic nephropathy, but few if any specific treatments for human diabetic nephropathy based on the mechanisms of disease initiation and progression have been clearly identified. Thus, it is important to investigate and determine pathogenesis (mechanisms of initiation and/or progression) and treatments using various experimental models of type 2 diabetic nephropathy. \u0000 \u0000This special issue contains 11 papers, based on studies of various animal models, cell cultures, and human samples. \u0000 \u0000In the paper entitled “Dietary restriction ameliorates diabetic nephropathy through anti-inflammatory effects and regulation of the autophagy via restoration of Sirt1 in diabetic Wistar fatty (fa/fa) rats: a model of type 2 diabetes,” M. Kitada et al. examined the renoprotective effects of dietary restriction (DR) in Wistar fatty (fa/fa) rats (WFRs). DR ameliorated renal abnormalities including inflammation in WFRs. The decrease in Sirt1 levels, increase in acetylated-NF-κB, and impaired autophagy in WFRs were improved by DR. The authors concluded that DR exerted anti-inflammatory effects and improved the dysregulation of autophagy through the restoration of Sirt1 in the kidneys of WFRs, which resulted in the amelioration of renal injuries in type 2 diabetes. \u0000 \u0000In the paper entitled “High glucose increases metallothionein expression in renal proximal tubular epithelial cells,” D. Ogawa et al. found that the renal tissues in adult male diabetic rats induced by streptozotocin were stained with antibodies for MT-1/-2. MT-1/-2 expression was also evaluated in mProx24 cells, a mouse renal proximal tubular epithelial cell line, stimulated with high glucose medium and pretreated with the antioxidant vitamin E. These observations suggest that MT-1/-2 is induced in renal proximal tubular epithelial cells as an antioxidant to protect the kidney from oxidative stress and that it may offer a novel therapeutic target against diabetic nephropathy. \u0000 \u0000In the paper entitled “Targeted proteomics of isolated glomeruli from the kidneys of diabetic rats: sorbin and SH3 domain containing 2 is a novel protein associated with diabetic nephropathy,” S. Nakatani et al. examined the protein expression in the isolated glomeruli from spontaneous type 2 diabetic (OLETF) rats and their age-matched control littermates (LETO) in the early and","PeriodicalId":12109,"journal":{"name":"Experimental Diabetes Research","volume":"2012 ","pages":"218917"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/218917","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30549911","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}