Experimental Diabetes Research最新文献

{"title":"Associations of common variants at APLN and hypertension in Chinese subjects with and without diabetes.","authors":"Rong Zhang,&nbsp;Jingyi Lu,&nbsp;Cheng Hu,&nbsp;Congrong Wang,&nbsp;Weihui Yu,&nbsp;Feng Jiang,&nbsp;Shanshan Tang,&nbsp;Yuqian Bao,&nbsp;Kunsan Xiang,&nbsp;Weiping Jia","doi":"10.1155/2012/917496","DOIUrl":"https://doi.org/10.1155/2012/917496","url":null,"abstract":"<p><strong>Background: </strong>Apelin, the endogenous ligand for the APJ receptor, has a potent hypotensive effect via a nitric oxide-dependent mechanism in vivo. The aim of the study was to investigate the association between the common variants of apelin gene (APLN) and hypertension, which was reported recently in a Chinese Han population with and without diabetes.</p><p><strong>Methods: </strong>Three single nucleotide polymorphisms (SNPs) on APLN were genotyped in 3156 diabetic patients and 3736 nondiabetic individuals. For non-diabetic subjects, 1779 were enrolled in stage 1 and 1757 were recruited for validation. A meta-analysis combining the two stages was carried out to obtain the overall effect.</p><p><strong>Results: </strong>In diabetic patients, no significant associations of the three SNPs with hypertension were observed. In contrast, we found that rs2235306 was associated with hypertension in non-diabetic males after adjusting for covariates (OR = 1.19, P = 0.039) while rs2235307 and rs3115759 displayed no evidence of association in both genders. One haplotype, C-C-A, also showed an association with hypertension (OR = 1.47, P = 0.032) only in men. However, analysis in stage 2 and meta-analysis did not support these findings.</p><p><strong>Conclusions: </strong>We conclude that common variants on APLN are not associated with the prevalence of hypertension in the Chinese.</p>","PeriodicalId":12109,"journal":{"name":"Experimental Diabetes Research","volume":"2012 ","pages":"917496"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/917496","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31159649","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":"Prevalence and risk factors of prolonged QTc interval among Chinese patients with type 2 diabetes.","authors":"Xiang Li,&nbsp;Hui Ren,&nbsp;Zhang-rong Xu,&nbsp;Yan-jun Liu,&nbsp;Xiao-pin Yang,&nbsp;Jian-qin Liu","doi":"10.1155/2012/234084","DOIUrl":"https://doi.org/10.1155/2012/234084","url":null,"abstract":"<p><strong>Objectives: </strong>The aim of this study was to evaluate the prevalence and the risk factors of prolonged QTc interval among Chinese patients with type 2 diabetes.</p><p><strong>Methods: </strong>The retrospective study included 3156 outpatients from the Diabetes Centre, the 306th Hospital of PLA, during the period from September 2003 to June 2010. QT interval was measured manually in the 12-lead conventional electrocardiogram. The QT interval corrected for heart rate (QTc) was calculated using Bazett's formula. Additional demographic and laboratory data were also collected. Potential risk factors of prolonged QTc interval were assessed using multivariable regression.</p><p><strong>Results: </strong>The prevalence of prolonged QTc interval among Chinese patients with type 2 diabetes was 30.1%. Height (OR 0.156, 95% CI 0.032~0.748), waist circumference (OR 1.025, 95% CI 1.010~1.040), diastolic blood pressure (OR 1.016, 95% CI 1.007~1.026), postprandial glucose (OR 1.040, 95% CI 1.022~1.059), fasting insulin (OR 1.014, 95% CI 1.003~1.025), and presence of microalbuminuria (OR 1.266, 95% CI 1.033~1.551) were significant risk factors.</p><p><strong>Conclusions: </strong>The prevalence of prolonged QTc interval among Chinese patients with type 2 diabetes is high. Risk factors for prolongation of QTc interval were low height, high waist circumference, increasing diastolic blood pressure levels, high postprandial glucose levels, high fasting insulin levels, and presence of microalbuminuria.</p>","PeriodicalId":12109,"journal":{"name":"Experimental Diabetes Research","volume":"2012 ","pages":"234084"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/234084","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31161738","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":"Nicotine exposure exacerbates development of cataracts in a type 1 diabetic rat model.","authors":"Nima Tirgan,&nbsp;Gabriela A Kulp,&nbsp;Praveena Gupta,&nbsp;Adam Boretsky,&nbsp;Tomasz A Wiraszka,&nbsp;Bernard Godley,&nbsp;Ronald G Tilton,&nbsp;Massoud Motamedi","doi":"10.1155/2012/349320","DOIUrl":"https://doi.org/10.1155/2012/349320","url":null,"abstract":"<p><p>Diabetes and smoking are known risk factors for cataract development. In this study, we evaluated the effect of nicotine on the progression of cataracts in a type 1 diabetic rat model. Diabetes was induced in Sprague-Dawley rats by a single injection of 65 mg/kg streptozotocin. Daily nicotine injections were administered subcutaneously. Forty-five rats were divided into groups of diabetics with and without nicotine treatment and controls with and without nicotine treatment. Progression of lens opacity was monitored using a slit lamp biomicroscope and scores were assigned. To assess whether systemic inflammation played a role in mediating cataractogenesis, we studied serum levels of eotaxin, IL-6, and IL-4. The levels of the measured cytokines increased significantly in nicotine-treated and untreated diabetic animals versus controls and demonstrated a positive trend in the nicotine-treated diabetic rats. Our data suggest the presence of a synergistic relationship between nicotine and diabetes that accelerated cataract formation via inflammatory mediators.</p>","PeriodicalId":12109,"journal":{"name":"Experimental Diabetes Research","volume":"2012 ","pages":"349320"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/349320","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30965369","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":"Short-chain fatty acid propionate alleviates Akt2 knockout-induced myocardial contractile dysfunction.","authors":"Linlin Li,&nbsp;Yinan Hua,&nbsp;Jun Ren","doi":"10.1155/2012/851717","DOIUrl":"https://doi.org/10.1155/2012/851717","url":null,"abstract":"<p><p>BACKGROUND AND AIMS. Dysregulation of Akt has been implicated in diseases such as cancer and diabetes, although little is known about the role of Akt deficiency on cardiomyocyte contractile function. This study was designed to examine the effect of Akt2 knockout-induced cardiomyocyte contractile response and the effect of dietary supplementation of short-chain fatty acid propionate on Akt2 knockout-induced cardiac dysfunction, if any. METHODS AND RESULTS. Adult male wild-type (WT) and Akt2 knockout mice were treated with propionate (0.3 g/kg, p.o.) or vehicle for 7 days. Oral glucose tolerance test (OGTT) was performed. Cardiomyocyte contractile function and mitochondrial membrane potential were assessed. Expression of insulin-signaling molecules Akt, PTEN, GSK3β, and eNOS receptors for short-chain fatty acids GPR41, and GPR43 as well as protein phosphatase PP2AA, PP2AB, PP2C were evaluated using Western blot analysis. Our results revealed that Akt2 knockout led to overt glucose intolerance, compromised cardiomyocyte contractile function (reduced peak shortening and maximal velocity of shortening/relengthening as well as prolonged relengthening), loss of mitochondrial membrane potential, decreased GPR41 and elevated GPR43 expression, all of which, with the exception of glucose intolerance and elevated GPR43 level, were significantly attenuated by propionate. Neither Akt2 knockout nor propionate affected the expression of protein phosphatases, eNOS, pan, and phosphorylated PTEN and GSK3β. CONCLUSIONS. Taken together, these data depicted that Akt2 knockout may elicit cardiomyocyte contractile and mitochondrial defects and a beneficial role of propionate or short-chain fatty acids against Akt2 deficiency-induced cardiac anomalies.</p>","PeriodicalId":12109,"journal":{"name":"Experimental Diabetes Research","volume":"2012 ","pages":"851717"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/851717","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30176071","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":"Diabetes and nonalcoholic fatty liver disease.","authors":"Konstantinos Kantartzis,&nbsp;Amalia Gastaldelli,&nbsp;Faidon Magkos,&nbsp;Jean-Marc Lavoie","doi":"10.1155/2012/404632","DOIUrl":"https://doi.org/10.1155/2012/404632","url":null,"abstract":"With almost every third individual affected in the general population in industrialized countries and increasing prevalence among children and adolescents, nonalcoholic fatty liver disease (NAFLD) represents the most common cause of chronic liver diseases such as cirrhosis, liver failure, and hepatocellular carcinoma and is therefore the most common cause of liver transplantation. In addition, in recent years NAFLD has emerged as a key player in human metabolism. Several studies demonstrate that NAFLD is strongly associated with insulin resistance and precedes the manifestation of type 2 diabetes and cardiovascular disease. \u0000 \u0000Of particular interest, the associations of ectopic fat accumulation in the liver with insulin resistance and type 2 diabetes are stronger than the respective of visceral and intramyocellular fat, implying that liver fat is an independent factor modifying the whole-body obesity-related metabolic risk. Thus, fatty liver may be not simply another manifestation of the metabolic syndrome, but it may itself induce or worsen insulin resistance and type 2 diabetes. In other words, fatty liver may be a determinant, not merely a marker of metabolic dysfunction. Though certainly, cause-and-effect relationships are hard to establish. \u0000 \u0000It is therefore why a concerted effort of the academic disciplines is requested to study the responsible mechanisms involved in the process of hepatic fat accumulation as well as the mechanisms regulating the crosstalk between fatty liver and other tissues important for regulation of metabolism in humans. In this special issue, we have invited some papers hoping to shed light on some aspects of this very interesting field. \u0000 \u0000In the first paper of this issue “Diagnosis and evaluation of nonalcoholic fatty liver disease,” epidemiology and tools for diagnosing NAFLD are reviewed. Regarding epidemiology, interesting data are provided on the interaction of NAFLD and type 2 diabetes, when concurrently present. In terms of diagnostic evaluation, of particular interest is the systematic presentation of old and novel biomarkers as well as panel markers (scores) and their sensitivity, specificity, positive and negative predictive values in estimating the amount of liver fat and differentiating more progressive forms of NAFLD, such as NASH and fibrosis, from simple steatosis. \u0000 \u0000The second paper of this issue “Role of transcription factor modifications in the pathogenesis of insulin resistance,” evaluates the diverse types of posttranslational modification of transcription factors in insulin-sensitive tissues and their putative role in the pathogenesis of insulin resistance. The authors particularly focused on the liver, where a lot of transcription factors have key roles in metabolic pathways critical for the pathogenesis of hepatic insulin resistance and NAFLD. For instance, forkhead box protein 1 (FOXO1) and cAMP response element binding protein (CREB) are major transcription factors for gluconeogenic gene ex","PeriodicalId":12109,"journal":{"name":"Experimental Diabetes Research","volume":"2012 ","pages":"404632"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/404632","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30346152","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":"Diabetes and thyroid cancer risk: literature review.","authors":"Shyang-Rong Shih,&nbsp;Wei-Yih Chiu,&nbsp;Tien-Chun Chang,&nbsp;Chin-Hsiao Tseng","doi":"10.1155/2012/578285","DOIUrl":"https://doi.org/10.1155/2012/578285","url":null,"abstract":"<p><p>Diabetic patients have a higher risk of various types of cancer. However, whether diabetes may increase the risk of thyroid cancer has not been extensively studied. This paper reviews and summarizes the current literature studying the relationship between diabetes mellitus and thyroid cancer, and the possible mechanisms linking such an association. Epidemiologic studies showed significant or nonsignificant increases in thyroid cancer risk in diabetic women and nonsignificant increase or no change in thyroid cancer risk in diabetic men. A recent pooled analysis, including 5 prospective studies from the USA, showed that the summary hazard ratio (95% confidence interval) for women was 1.19 (0.84-1.69) and was 0.96 (0.65-1.42) for men. Therefore, the results are controversial and the association between diabetes and thyroid cancer is probably weak. Further studies are necessary to confirm their relationship. Proposed mechanisms for such a possible link between diabetes and thyroid cancer include elevated levels of thyroid-stimulating hormone, insulin, glucose and triglycerides, insulin resistance, obesity, vitamin D deficiency, and antidiabetic medications such as insulin or sulfonylureas.</p>","PeriodicalId":12109,"journal":{"name":"Experimental Diabetes Research","volume":"2012 ","pages":"578285"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/578285","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30750382","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":"Impact of maternal diabetes on epigenetic modifications leading to diseases in the offspring.","authors":"Nikolaos Vrachnis,&nbsp;Nikolaos Antonakopoulos,&nbsp;Zoe Iliodromiti,&nbsp;Konstantinos Dafopoulos,&nbsp;Charalambos Siristatidis,&nbsp;Kalliopi I Pappa,&nbsp;Efthymios Deligeoroglou,&nbsp;Nicolaos Vitoratos","doi":"10.1155/2012/538474","DOIUrl":"https://doi.org/10.1155/2012/538474","url":null,"abstract":"<p><p>Gestational diabetes, occurring during the hyperglycemic period of pregnancy in maternal life, is a pathologic state that increases the incidence of complications in both mother and fetus. Offspring thus exposed to an adverse fetal and early postnatal environment may manifest increased susceptibility to a number of chronic diseases later in life. Compelling evidence for the role of epigenetic transmission in these complications has come from comparison of siblings born before and after the development of maternal diabetes, exposure to this intrauterine diabetic environment being shown to cause alterations in fetal growth patterns which predispose these infants to developing overweight and obesity later in life. Diabetes of the offspring is also mainly the consequence of exposure to the diabetic intrauterine environment, in addition to genetic susceptibility. Since obesity and diabetes are known to increase the risk of cardiovascular disease, cardiovascular sequelae in the offspring of diabetic mothers are virtually inevitable. Research data also suggest that exposure to a diabetic intrauterine environment during pregnancy is associated with an increase in dyslipidemia, subclinical vascular inflammation, and endothelial dysfunction processes in the offspring, all of which are linked with development of cardiovascular disease later in life. The main underlying mechanisms involve persistent hyperglycemia hyperinsulinemia and leptin resistance.</p>","PeriodicalId":12109,"journal":{"name":"Experimental Diabetes Research","volume":"2012 ","pages":"538474"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/538474","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31109056","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":"Small molecule drug discovery at the glucagon-like peptide-1 receptor.","authors":"Francis S Willard,&nbsp;Ana B Bueno,&nbsp;Kyle W Sloop","doi":"10.1155/2012/709893","DOIUrl":"https://doi.org/10.1155/2012/709893","url":null,"abstract":"<p><p>The therapeutic success of peptide glucagon-like peptide-1 (GLP-1) receptor agonists for the treatment of type 2 diabetes mellitus has inspired discovery efforts aimed at developing orally available small molecule GLP-1 receptor agonists. Although the GLP-1 receptor is a member of the structurally complex class B1 family of GPCRs, in recent years, a diverse array of orthosteric and allosteric nonpeptide ligands has been reported. These compounds include antagonists, agonists, and positive allosteric modulators with intrinsic efficacy. In this paper, a comprehensive review of currently disclosed small molecule GLP-1 receptor ligands is presented. In addition, examples of \"ligand bias\" and \"probe dependency\" for the GLP-1 receptor are discussed; these emerging concepts may influence further optimization of known molecules or persuade designs of expanded screening strategies to identify novel chemical starting points for GLP-1 receptor drug discovery.</p>","PeriodicalId":12109,"journal":{"name":"Experimental Diabetes Research","volume":"2012 ","pages":"709893"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/709893","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30631235","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":"Mitochondrial dysregulation in the pathogenesis of diabetes: potential for mitochondrial biogenesis-mediated interventions.","authors":"Anna-Maria Joseph,&nbsp;Denis R Joanisse,&nbsp;Richard G Baillot,&nbsp;David A Hood","doi":"10.1155/2012/642038","DOIUrl":"https://doi.org/10.1155/2012/642038","url":null,"abstract":"<p><p>Muscle mitochondrial metabolism is a tightly controlled process that involves the coordination of signaling pathways and factors from both the nuclear and mitochondrial genomes. Perhaps the most important pathway regulating metabolism in muscle is mitochondrial biogenesis. In response to physiological stimuli such as exercise, retrograde signaling pathways are activated that allow crosstalk between the nucleus and mitochondria, upregulating hundreds of genes and leading to higher mitochondrial content and increased oxidation of substrates. With type 2 diabetes, these processes can become dysregulated and the ability of the cell to respond to nutrient and energy fluctuations is diminished. This, coupled with reduced mitochondrial content and altered mitochondrial morphology, has been directly linked to the pathogenesis of this disease. In this paper, we will discuss our current understanding of mitochondrial dysregulation in skeletal muscle as it relates to type 2 diabetes, placing particular emphasis on the pathways of mitochondrial biogenesis and mitochondrial dynamics, and the therapeutic value of exercise and other interventions.</p>","PeriodicalId":12109,"journal":{"name":"Experimental Diabetes Research","volume":"2012 ","pages":"642038"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/642038","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30353515","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":"Increased caspase-3 immunoreactivity of erythrocytes in STZ diabetic rats.","authors":"Uğur Fırat,&nbsp;Savaş Kaya,&nbsp;Abdullah Cim,&nbsp;Hüseyin Büyükbayram,&nbsp;Osman Gökalp,&nbsp;Mehmet Sinan Dal,&nbsp;Mehmet Numan Tamer","doi":"10.1155/2012/316384","DOIUrl":"https://doi.org/10.1155/2012/316384","url":null,"abstract":"<p><p>Eryptosis is a term to define apoptosis of erythrocytes. Oxidative stress and hyperglycemia, both of which exist in the diabetic intravascular environment, can trigger eryptosis of erythrocytes. In this experimental study, it is presented that the majority of erythrocytes shows caspase-3 immunoreactivity in streptozocin- (STZ)-induced diabetic rats. Besides that, caspase-3 positive erythrocytes are aggregated and attached to vascular endothelium. In conclusion, these results may start a debate that eryptosis could have a role in the diabetic complications.</p>","PeriodicalId":12109,"journal":{"name":"Experimental Diabetes Research","volume":"2012 ","pages":"316384"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/316384","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30631233","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}