{"title":"Emerging pharmacotherapies for diabetic macular edema.","authors":"Golnaz Javey, Stephen G Schwartz, 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}
Min Zhang, Hai-Ming Zhao, Zhen-Ying Qin, Rui Qin, Xiao-Hui Chen, Ya-Ping Zhao, Chun-Mei Zhang, Chun-Lin Gao, Chun Zhu, Chen-Bo Ji, Xin-Guo Cao, Xi-Rong Guo
{"title":"Regulation of LYRM1 gene expression by free fatty acids, adipokines, and rosiglitazone in 3T3-L1 adipocytes.","authors":"Min Zhang, Hai-Ming Zhao, Zhen-Ying Qin, Rui Qin, Xiao-Hui Chen, Ya-Ping Zhao, Chun-Mei Zhang, Chun-Lin Gao, Chun Zhu, Chen-Bo Ji, Xin-Guo Cao, 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, Ismeet Kaur, Rubina Tabassum, Om Prakash Dwivedi, Saurabh Ghosh, Nikhil Tandon, 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, Michal Sapák, 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}
Danielle Senador, Swapnil Shewale, Maria Claudia Irigoyen, Khalid M Elased, Mariana Morris
{"title":"Effects of restricted fructose access on body weight and blood pressure circadian rhythms.","authors":"Danielle Senador, Swapnil Shewale, Maria Claudia Irigoyen, Khalid M Elased, 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}
Yasuhiko Tomino, Mark E Cooper, Theodore W Kurtz, Yoshio Shimizu
{"title":"Experimental models of type-2 diabetic nephropathy.","authors":"Yasuhiko Tomino, Mark E Cooper, Theodore W Kurtz, 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}
Wen-Ko Chiou, Jawl-Shan Hwang, Kuang-Hung Hsu, Jen-Der Lin
{"title":"Diabetes mellitus increased mortality rates more in gender-specific than in nongender-specific cancer patients: a retrospective study of 149,491 patients.","authors":"Wen-Ko Chiou, Jawl-Shan Hwang, Kuang-Hung Hsu, Jen-Der Lin","doi":"10.1155/2012/701643","DOIUrl":"https://doi.org/10.1155/2012/701643","url":null,"abstract":"<p><strong>Aims: </strong>Hyperinsulinemia in overweight status, obesity, and type 2 diabetes mellitus (DM) is often accompanied by cancer. Gender is important in cancer epidemiology, clinical presentation, and response to therapy in different histological types of malignancy. Insufficient information is available concerning gender differences in DM with organ-specific and nonorgan-specific cancers. This study aimed to analyze gender differences in hospitalized cancer patients with or without type 2 DM.</p><p><strong>Methods: </strong>We retrospectively reviewed ten years of patients hospitalized in one institution, enrolling 36,457 female and 50,004 male cancer patients of which 5,992 females and 8,345 males were diagnosed as type 2 DM.</p><p><strong>Results: </strong>Statistically significant increases in incidence of type 2 DM were found in patients of both genders with pancreatic, liver, and urinary tract cancer. Increased incidence of type 2 DM was found in lung and hematologic malignancies in females and prostate cancer in males. Increases in mortality rates of females with type 2 DM (2.98%) were higher than those in males. DM increased mortality rates in gender-specific cancers from 1.91% (uterus, HR: 1.33) to 5.04% (ovary, HR: 1.49).</p><p><strong>Conclusion: </strong>Type 2 DM increased mortality of cancer patients of both genders, with higher increases in gender-specific than in nongender-specific cancers.</p>","PeriodicalId":12109,"journal":{"name":"Experimental Diabetes Research","volume":"2012 ","pages":"701643"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/701643","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30693545","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":"Cardiovascular benefits of GLP-1-based herapies in patients with diabetes mellitus type 2: effects on endothelial and vascular dysfunction beyond glycemic control.","authors":"Thomas Forst, Matthias M Weber, Andreas Pfützner","doi":"10.1155/2012/635472","DOIUrl":"https://doi.org/10.1155/2012/635472","url":null,"abstract":"<p><p>Type 2 diabetes mellitus (T2DM) is a progressive multisystemic disease accompanied by vascular dysfunction and a tremendous increase in cardiovascular mortality. Numerous adipose-tissue-derived factors and beta cell dysfunction contribute to the increased cardiovascular risk in patients with T2DM. Nowadays, numerous pharmacological interventions are available to lower blood glucose levels in patients with type 2 diabetes. Beside more or less comparable glucose lowering efficacy, some of them have shown limited or probably even unfavorable effects on the cardiovascular system and overall mortality. Recently, incretin-based therapies (GLP-1 receptor agonists and DPP-IV inhibitors) have been introduced in the treatment of T2DM. Beside the effects of GLP-1 on insulin secretion, glucagon secretion, and gastrointestinal motility, recent studies suggested a couple of direct cardiovascular effects of GLP-1-based therapies. The goal of this paper is to provide an overview about the current knowledge of direct GLP-1 effects on endothelial and vascular function and potential consequences on the cardiovascular outcome in patients with T2DM treated with GLP-1 receptor agonists or DPP-IV inhibitors.</p>","PeriodicalId":12109,"journal":{"name":"Experimental Diabetes Research","volume":"2012 ","pages":"635472"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/635472","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30609744","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}
Karen J Nickelson, Kelly L Stromsdorfer, R Taylor Pickering, Tzu-Wen Liu, Laura C Ortinau, Aileen F Keating, James W Perfield
{"title":"A comparison of inflammatory and oxidative stress markers in adipose tissue from weight-matched obese male and female mice.","authors":"Karen J Nickelson, Kelly L Stromsdorfer, R Taylor Pickering, Tzu-Wen Liu, Laura C Ortinau, Aileen F Keating, James W Perfield","doi":"10.1155/2012/859395","DOIUrl":"https://doi.org/10.1155/2012/859395","url":null,"abstract":"<p><p>Expansion of intra-abdominal adipose tissue and the accompanying inflammatory response has been put forward as a unifying link between obesity and the development of chronic diseases. However, an apparent sexual dimorphism exists between obesity and chronic disease risk due to differences in the distribution and abundance of adipose tissue. A range of experimental protocols have been employed to demonstrate the role of estrogen in regulating health benefits; however, most studies are confounded by significant differences in body weight and adiposity. Therefore, the purpose of this study was to compare weight-matched obese male and female mice to determine if the sex-dependent health benefits remain when body weight is similar. The development of obesity in female mice receiving a high-fat diet was delayed; however, subsequent comparisons of weight-matched obese mice revealed greater adiposity in obese female mice. Despite excess adiposity and enlarged adipocyte size, obese females remained more glucose tolerant than weight-matched male mice, and this benefit was associated with increased expression of adiponectin and reductions in immune cell infiltration and oxidative stress in adipose tissue. Therefore, the protective benefits of estrogen persist in the obese state and appear to improve the metabolic phenotype of adipose tissue and the individual.</p>","PeriodicalId":12109,"journal":{"name":"Experimental Diabetes Research","volume":"2012 ","pages":"859395"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/859395","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30750384","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}