Experimental Diabetes Research最新文献

{"title":"Genetic dissection of complex genetic factor involved in NIDDM of OLETF rat.","authors":"Takahisa Yamada,&nbsp;Hiroyuki Kose,&nbsp;Takeshi Ohta,&nbsp;Kozo Matsumoto","doi":"10.1155/2012/582546","DOIUrl":"https://doi.org/10.1155/2012/582546","url":null,"abstract":"<p><p>The Otsuka Long-Evans Tokushima Fatty (OLETF) rat is an animal model for obese-type, noninsulin-dependent diabetes mellitus (NIDDM) in humans. NIDDM in this rat model was shown to be regulated by multiple genes. We have identified 14 quantitative trait loci (QTLs) responsible for NIDDM (Nidd1-14/of) on chromosomes 1, 5, 7, 8, 9, 11, 12, 14, 16, and 17 by a whole genome search in 160 F2 progenies obtained by mating the OLETF and the F344 rats. Among these loci, two QTLs, Nidd1 and 2/of, were declared significant loci at a genome-wide level. Nidd3, 8, 9, and 13/of exhibited heterosis: heterozygotes showing significantly higher glucose levels than OLETF or F344 homozygotes. We also found evidence for interaction (epistasis) between Nidd1/of and Nidd2/of, between Nidd1/of and Nidd10/of, between Nidd2/of and Nidd8/of, and between Nidd2/of and Nidd14/of. Furthermore, Nidd6 and 11/of showed linkage with body weight, and Nidd1, 2, 8, 9, 10, and 12/of had an interaction with body weight. These indicated that NIDDM in the OLETF would have a higher degree of genetic complexity. We suggest several interesting candidate genes located in rat genomic regions for Nidd1-14/of or the syntenic regions in human genome.</p>","PeriodicalId":12109,"journal":{"name":"Experimental Diabetes Research","volume":"2012 ","pages":"582546"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/582546","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31019493","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":"Haplotypes in the CRP gene associated with increased BMI and levels of CRP in subjects with type 2 diabetes or obesity from Southwestern Mexico.","authors":"América Martínez-Calleja,&nbsp;Irma Quiróz-Vargas,&nbsp;Isela Parra-Rojas,&nbsp;José Francisco Muñoz-Valle,&nbsp;Marco A Leyva-Vázquez,&nbsp;Gloria Fernández-Tilapa,&nbsp;Amalia Vences-Velázquez,&nbsp;Miguel Cruz,&nbsp;Eduardo Salazar-Martínez,&nbsp;Eugenia Flores-Alfaro","doi":"10.1155/2012/982683","DOIUrl":"https://doi.org/10.1155/2012/982683","url":null,"abstract":"<p><strong>Objective: </strong>We evaluated the association between four polymorphisms in the CRP gene with circulating levels of C-reactive protein (CRP), type 2 diabetes (T2D), obesity, and risk score of coronary heart disease.</p><p><strong>Methods: </strong>We studied 402 individuals and classified them into four groups: healthy, obese, T2D obese, and T2D without obesity, from Guerrero, Southwestern Mexico. Blood levels of CRP, glucose, cholesterol, triglycerides, and leukocytes were measured. Genotyping was performed by PCR/RFLP, and the risk score for coronary heart disease was determined by the Framingham's methodology.</p><p><strong>Results: </strong>The TT genotype of SNP rs1130864 was associated with increased body mass index and T2D patients with obesity. We found that the haplotype 2 (TGAG) was associated with increased levels of CRP (β = 0.3; 95%CI: 0.1, 0.5; P = 0.005) and haplotype 7 (TGGG) with higher body mass index (BMI) (β = 0.2; 95%CI: 0.1, 0.3; P < 0.001). The risk score for coronary heart disease was associated with increased levels of CRP, but not with any polymorphism or haplotype.</p><p><strong>Conclusions: </strong>The association between the TT genotype of SNP rs1130864 with obesity and the haplotype 7 with BMI may explain how obesity and genetic predisposition increase the risk of diseases such as T2D in the population of Southwestern Mexico.</p>","PeriodicalId":12109,"journal":{"name":"Experimental Diabetes Research","volume":"2012 ","pages":"982683"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/982683","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30964116","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":"Dysfunctional endothelial progenitor cells in metabolic syndrome.","authors":"Sridevi Devaraj, Ishwarlal Jialal","doi":"10.1155/2012/585018","DOIUrl":"10.1155/2012/585018","url":null,"abstract":"<p><p>The metabolic syndrome (MetS) is highly prevalent and confers an increased risk of diabetes and cardiovascular disease. A key early event in atherosclerosis is endothelial dysfunction. Numerous groups have reported endothelial dysfunction in MetS. However, the measurement of endothelial function is far from optimum. There has been much interest recently in a subtype of progenitor cells, termed endothelial progenitor cells (EPCs), that can circulate, proliferate, and dfferentiate into mature endothelial cells. EPCs can be characterized by the assessment of surface markers, CD34 and vascular endothelial growth factor receptor-2, VEGFR-2 (KDR). The CD34(+)KDR(+) phenotype has been demonstrated to be an independent predictor of cardiovascular outcomes. MetS patients without diabetes or cardiovascular diseases have decreased EPC number and functionality as evidenced by decreased numbers of colony forming units, decreased adhesion and migration, and decreased tubule formation. Strategies that have been shown to upregulate and enhance EPC number and functionality include statins, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, and peroxisome-proliferator-activating-receptor gamma agonists. Mechanisms by which they affect EPC number and functionality need to be studied. Thus, EPC number and/or functionality could emerge as novel cellular biomarkers of endothelial dysfunction and cardiovascular disease risk in MetS.</p>","PeriodicalId":12109,"journal":{"name":"Experimental Diabetes Research","volume":"2012 ","pages":"585018"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3176409/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30015817","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":"Endoplasmic reticulum stress in the β-cell pathogenesis of type 2 diabetes.","authors":"Sung Hoon Back,&nbsp;Sang-Wook Kang,&nbsp;Jaeseok Han,&nbsp;Hun-Taeg Chung","doi":"10.1155/2012/618396","DOIUrl":"https://doi.org/10.1155/2012/618396","url":null,"abstract":"<p><p>Type 2 diabetes is a complex metabolic disorder characterized by high blood glucose in the context of insulin resistance and relative insulin deficiency by β-cell failure. Even if the mechanisms underlying the pathogenesis of β-cell failure are still under investigation, recent increasing genetic, experimental, and clinical evidence indicate that hyperactivation of the unfolded protein response (UPR) to counteract metabolic stresses is closely related to β-cell dysfunction and apoptosis. Signaling pathways of the UPR are \"a double-edged sword\" that can promote adaptation or apoptosis depending on the nature of the ER stress condition. In this paper, we summarized our current understanding of the mechanisms and components related to ER stress in the β-cell pathogenesis of type 2 diabetes.</p>","PeriodicalId":12109,"journal":{"name":"Experimental Diabetes Research","volume":"2012 ","pages":"618396"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/618396","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30139889","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":"Mannan-binding lectin in diabetic kidney disease: the impact of mouse genetics in a type 1 diabetes model.","authors":"Jakob Appel Østergaard,&nbsp;Mette Bjerre,&nbsp;Satish Posettihalli RamachandraRao,&nbsp;Kumar Sharma,&nbsp;Jens Randel Nyengaard,&nbsp;Troels Krarup Hansen,&nbsp;Steffen Thiel,&nbsp;Allan Flyvbjerg","doi":"10.1155/2012/678381","DOIUrl":"https://doi.org/10.1155/2012/678381","url":null,"abstract":"<p><strong>Unlabelled: </strong>BACKGROUND. Mannan-binding lectin (MBL) is involved in the development of diabetic nephropathy. MBL is a part of the innate immune system where it can activate the complement system. Serum MBL level predicts later renal impairment in diabetes patients. Direct involvement of MBL in the development of diabetic kidney disease is observed in one animal strain. However, this involvement may differ among the animal strains. We thus examined the impact of the genetic background on the role of MBL in diabetic nephropathy.</p><p><strong>Materials/methods: </strong>C57BL/6JBomTac and 129S6/SvEvTac mice were compared. In both strains, experimental type 1 diabetes was induced in wild-type (WT) and MBL-knockout (MBL-KO) mice by streptozotocin. Nondiabetic WT and MBL-KO mice were used as controls. We tested if MBL modified the diabetes-induced kidney changes by two-way ANOVA allowing for interaction.</p><p><strong>Results: </strong>MBL aggravated diabetes-induced kidney growth and glomerulus enlargement in C57BL/6JBomTac mice. MBL did not modify diabetes effects on glomerular basement membrane thickness or mesangial volume in any strain. Diabetes-induced changes in renal gene transcription of growth factors and matrix components were unaffected by MBL.</p><p><strong>Conclusions: </strong>Strain-specific MBL effects were found on downstream diabetic kidney changes. This emphasizes the importance of genetic background in this model of diabetic complications.</p>","PeriodicalId":12109,"journal":{"name":"Experimental Diabetes Research","volume":"2012 ","pages":"678381"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/678381","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30653180","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":"Molecular intricacies and the role of ER stress in diabetes.","authors":"Muthuswamy Balasubramanyam,&nbsp;Lalit P Singh,&nbsp;Sampathkumar Rangasamy","doi":"10.1155/2012/958169","DOIUrl":"https://doi.org/10.1155/2012/958169","url":null,"abstract":"Diabetes mellitus is a metabolic disease caused by both genetic and environmental factors. The pathogenic mechanism(s) of diabetes are complex, and the complicated networks related to this disease involve distinct signaling pathways. Evidence has recently been provided that ER stress might be involved in the pathogenesis of diabetes and its complications. Early steps in the maturation of secretory proteins take place in the ER, for example, the folding of the nascent polypeptide chains and posttranslational modifications important for proper folding and function of the protein. At a stage (due to several metabolic disturbances), when unfolded polypeptide exceeds the folding and/or processing capacity of the ER, cells are susceptible to a phenomenon referred to as “ER stress.” Under these conditions, specific signaling pathways, termed the unfolded protein response (UPR), are activated to return the ER to its normal physiological state. Prolonged activation of the ER stress and the UPR can lead to cell pathology and subsequent tissue dysfunction. There is now ample evidence that the UPR is chronically activated in many disease states including diabetes and its complications. Therefore, a better understanding of the pathways regulating ER stress and UPR is warranted in order to be instrumental for the design of novel therapies for diabetes and its complications. \u0000 \u0000In this focused issue of the journal, we have assembled several invited reviews, from well-recognized experts in their fields, as well as original research articles. These reviews provide state-of-the-art knowledge dealing with several mechanisms not only related to the genesis of diabetes but also to its progression to diabetic complications, all of which potentially originate or converge from chronic ER stress. In addition, several excellent original research articles demonstrate novel pathophysiologic aspects of diabetes with mechanistic studies central to ER stress and give hope and directionality for identifying new drug targets and developing newer therapeutic measures. \u0000 \u0000Of all the professional secretory cells we possess, β-cells are the most sensitive to ER stress because of the large fluctuations in protein synthesis (including insulin) they face daily. M.-K. Kim et al. have reviewed how this “protein quality-control machinery” of the cell is responsible for appropriate insulin biosynthesis and how ER stress plays an important role in the impairment of insulin biosynthesis. J. Zhong et al. have summarized the status on how ER stress plays an essential role in autoimmune-mediated β-cell destruction and also pointed out how ER stress regulates the functionality of immune cells relevant to autoimmune progression during Type 1 diabetes development. In an attempt to improve islet transplantation in humans, the molecular mechanism of apoptosis in β cells of islets in the transplantation setting needs to be clearly understood. In this context, M. Wang et al. have discussed their origi","PeriodicalId":12109,"journal":{"name":"Experimental Diabetes Research","volume":"2012 ","pages":"958169"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/958169","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30693546","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":"Early degenerative effects of diabetes mellitus on pancreas, liver, and kidney in rats: an immunohistochemical study.","authors":"Mehmet Haligur,&nbsp;Senay Topsakal,&nbsp;Ozlem Ozmen","doi":"10.1155/2012/120645","DOIUrl":"https://doi.org/10.1155/2012/120645","url":null,"abstract":"<p><p>Liver and kidney commonly affected by diabetes in chronic cases but pathogenetic mechanisms are not fully understood in early stages of the disease. The aim of this study was to investigate the immunohistochemical expression of caspase-3, cyclooxygenase (COX)-1 and-2, calcium sensing receptor (CSR), and hypoxia inducible factor-1α (HIF-1α) in pancreas, liver, and kidney in streptozotocin (STZ) induced DM. Study group (n = 6) were received streptozotocin (50 mg/kg) and control group (n = 6) physiologic saline. The blood glucose and ketonuria were measured, and necropsy was performed on them on third, fourth, and fifth days. Immunohistochemistry revealed that marked increase in caspase-3 reaction pancreas, liver, and kidney in the study group than control group. COX-1 slightly increased in these organs in study group compared to controls. Immunohistochemically COX-2 reaction was markedly positive in liver and kidney, but slightly increased in pancreas. The most increased reaction was observed in CRS and all organs were markedly positive. HIF-1α expression was also increased but the reaction was more severe in pancreas than liver and kidney. This study indicated that degeneration starts in organs in early stages of the disease and the most effective route for degeneration related to increase of calcium influx and hypoxia upon cells in DM.</p>","PeriodicalId":12109,"journal":{"name":"Experimental Diabetes Research","volume":"2012 ","pages":"120645"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/120645","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30798470","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":"Propyl gallate plays a nephroprotective role in early stage of diabetic nephropathy associated with suppression of glomerular endothelial cell proliferation and angiogenesis.","authors":"Shaojiang Tian,&nbsp;Junming Tang,&nbsp;Huihui Liu,&nbsp;Liping Wang,&nbsp;Jianming Shen,&nbsp;Junfeng Li,&nbsp;Yanjie Gan","doi":"10.1155/2012/209567","DOIUrl":"https://doi.org/10.1155/2012/209567","url":null,"abstract":"<p><p>There is growing evidence suggesting that glomerular endothelial cell proliferation and angiogenesis may be responsible for the pathophysiological events in the early stage of diabetic nephropathy. This study was designed to investigate the factors related to glomerular endothelial cell proliferation and glomerular angiogenesis and assess the effect of propyl gallate on preventing these disorders in diabetic rats. We found that glomerular hypertrophy, glomerular mesangial matrix expansion, and albuminuria were significantly increased in DN rats. CD31+ endothelial cells significantly increased in glomerulus of diabetic rats. Double immunofluorescence staining showed some structurally defective vasculus tubes in glomerulus. Real-time PCR and western blot demonstrated the glomerular eNOS expression remained at the same level, while remarkable decreased NO productions and suppressed eNOS activities were observed in diabetic rats. Treatment with propyl gallate improved glomerular pathological changes, reduced endothelial cell proliferation, decreased albuminuria, and restored eNOS activity, but did not alter eNOS expression. These data suggest that endothelial cell proliferation and immature angiogenesis may be the contributors to progression of DN. Propyl gallate is a potential novel therapeutic agent on prevention of diabetic nephropathy.</p>","PeriodicalId":12109,"journal":{"name":"Experimental Diabetes Research","volume":"2012 ","pages":"209567"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/209567","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30913802","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":"Aspects of inflammation and oxidative stress in pediatric obesity and type 1 diabetes: an overview of ten years of studies.","authors":"Brian Tran,&nbsp;Stacy Oliver,&nbsp;Jaime Rosa,&nbsp;Pietro Galassetti","doi":"10.1155/2012/683680","DOIUrl":"https://doi.org/10.1155/2012/683680","url":null,"abstract":"<p><p>Obesity and type 1 diabetes (T1DM) are the two most common conditions of altered metabolism in children and adolescents. In both, similar long-term cardiovascular complications are known to occur, mediated in large part by underlying inflammatory and oxidative processes whose biochemical details remain relatively unclear. Through a series of experiments in these patient populations, over the last decade our laboratory has clarified a number of key issues in this field. Interestingly, while obese and type 1 diabetic children often differed in the specific type and magnitude of molecular alterations, in both groups a clear exaggeration of inflammatory and oxidative activation was detected when compared to healthy, age-matched controls. Our main findings include definition of resting and exercise-induced cytokine patterns and leukocyte profiles, patterns of activation of immune cells in vitro, and correlation of the magnitude of observed alterations with severity of obesity and quality of glycemic control. Further, we have identified a series of alterations in growth factor profiles during exercise that parallel inflammatory changes in obese children. This paper offers a concise overview of the salient results from this decade-long research effort.</p>","PeriodicalId":12109,"journal":{"name":"Experimental Diabetes Research","volume":"2012 ","pages":"683680"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/683680","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30997396","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":"Metformin stimulates FGF21 expression in primary hepatocytes.","authors":"Eva B Nygaard,&nbsp;Sara G Vienberg,&nbsp;Cathrine Ørskov,&nbsp;Harald S Hansen,&nbsp;Birgitte Andersen","doi":"10.1155/2012/465282","DOIUrl":"https://doi.org/10.1155/2012/465282","url":null,"abstract":"<p><p>Fibroblast growth factor 21 (FGF21) is a novel metabolic regulator of glucose and lipid metabolism; however, the exact mechanism of action and regulation of FGF21 is not fully understood. Metabolic status plays an important role in the regulation of FGF21, and we therefore examined whether metformin, an indirect AMPK-activator, regulates FGF21 expression in hepatocytes. FGF21 mRNA and protein expression were determined after incubation of primary cultured rat and human hepatocytes with metformin for 24 hours. To study the role of AMPK in the putative regulation of FGF21, hepatocytes were incubated with Compound C (an AMPK inhibitor) in the presence of metformin. A strong dose-dependent increase in FGF21 expression was observed in both rat and human hepatocytes treated with metformin. This effect was blocked by addition of the AMPK-inhibitor Compound C. The study shows that metformin is a potent inducer of hepatic FGF21 expression and that the effect of metformin seems to be mediated through AMPK activation. As FGF21 therapy normalizes blood glucose in animal models of type 2 diabetes, the induction of hepatic FGF21 by metformin might play an important role in metformin's antidiabetic effect.</p>","PeriodicalId":12109,"journal":{"name":"Experimental Diabetes Research","volume":"2012 ","pages":"465282"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/465282","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31020738","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}