International journal of experimental diabetes research最新文献

{"title":"Decreased Expression Of apM1 in Omental and Subcutaneous Adipose Tissue of Humans With Type 2 Diabetes","authors":"M. Statnick, L. Beavers, L. J. Conner, H. Corominola, Dwayne Johnson, C. Hammond, R. Rafaeloff-Phail, T. Seng, T. Suter, J. Sluka, E. Ravussin, R. Gadski, J. Caro","doi":"10.1155/EDR.2000.81","DOIUrl":"https://doi.org/10.1155/EDR.2000.81","url":null,"abstract":"We have screened a subtracted cDNA library in order to identify differentially expressed genes in omental adipose tissue of human patients with Type 2 diabetes. One clone (#1738) showed a marked reduction in omental adipose tissue from patients with Type 2 diabetes. Sequencing and BLAST analysis revealed clone #1738 was the adipocyte-specific secreted protein gene apM1 (synonyms ACRP30, AdipoQ, GBP28). Consistent with the murine orthologue, apM1 mRNA was expressed in cultured human adipocytes and not in preadipocytes. Using RT-PCR we confirmed that apM1 mRNA levels were significantly reduced in omental adipose tissue of obese patients with Type 2 diabetes compared with lean and obese normoglycemic subjects. Although less pronounced, apM1 mRNA levels were reduced in subcutaneous adipose tissue of Type 2 diabetic patients. Whereas the biological function of apM1 is presently unknown, the tissue specific expression, structural similarities to TNFα and the dysregulated expression observed in obese Type 2 diabetic patients suggest that this factor may play a role in the pathogenesis of insulin resistance and Type 2 diabetes.","PeriodicalId":14040,"journal":{"name":"International journal of experimental diabetes research","volume":"365 1","pages":"81 - 88"},"PeriodicalIF":0.0,"publicationDate":"2000-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76607349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correlation Between Pancreatic Islet Uncoupling Protein-2 (UCP2) mRNA Concentration And Insulin Status in Rats","authors":"N. Kassis, C. Bernard, A. Pusterla, L. Casteilla, Luc Pétnicaud, D. Richard, D. Ricquier, A. Ktorza","doi":"10.1155/EDR.2000.185","DOIUrl":"https://doi.org/10.1155/EDR.2000.185","url":null,"abstract":"Hypothesizing that UCP2 may influence insulin secretion by modifying the ATP/ADP ratio within pancreatic islets, we have investigated the expression of intraislet UCP2 gene in rats showing insulin oversecretion (non-diabetic Zucker fa/fa obese rats, glucose-infused Wistar rats) or insulin undersecretion (fasting and mildly diabetic rats). We found that in Zucker fa/fa obese rats, hyperinsulinemia (1222 ± 98 pmol/1 vs. 128 ± 22 pmol/1 in lean Zucker rats) was accompanied by a significant increase in UCP2 mRNA levels. In rat submitted to a 5 day infusion with glucose, hyperinsulinemia (1126 ± 101 pmol/l vs. 215 ± 25 pmol/1 in Wistar control rats), coincided with an enhanced intraislet UCP2 gene expression, whereas a 8h or a 2 day-infusion did not induce significant changes in UCP2 mRNA expression. In rats made hypoinsulinemic and mildly diabetic by the injection of a low dose of streptozotocin, and in 4-day-fasting rats (plasma insulin 28 ± 5 pmol/1) UCP2 gene expression was sharply decreased. A 3-day-fast was ineffective. The data show the existence of a time-dependent correlation between islet mRNA UCP2 and insulin that may be interpreted as an adaptative response to prolonged insulin excess.","PeriodicalId":14040,"journal":{"name":"International journal of experimental diabetes research","volume":"26 1","pages":"185 - 193"},"PeriodicalIF":0.0,"publicationDate":"2000-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87649430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic Differentiation of Tumor-derived Insulin-producing Cells Selected for Resistance to Diabetogenic Drugs","authors":"Konstantin Bloch, P. Vardi","doi":"10.1155/EDR.2000.233","DOIUrl":"https://doi.org/10.1155/EDR.2000.233","url":null,"abstract":"Differentiation therapy has been proposed as a new approach to selectively engage the process of tumor cell differentiation during chemotherapy of cancer. Our recent in vitro study suggests that such an approach can be extended and utilized for the selection of tumor-derived insulin-producing cells for transplantation. Repeated treatment with streptozotocin selected toxin resistant subpopulation of insulin producing tumor RINmS cells, characterized increased level of insulin content and secretion. In the present study RINmS cells were found to have higher glucose sensitivity and insulin response compared with parental RINm cells. In addition, compounds known to induce elevated level of cAMP beta-cells, such as isobutyl methyl xanthine, and forskolin, potentiated glucose-induced insulin secretion of RINmS, but had no effect on the naive parental RINm cells. These experiments suggest that differentiation therapy can be utilized for engineering insulin producing cells with improved defense and secretory mechanisms.","PeriodicalId":14040,"journal":{"name":"International journal of experimental diabetes research","volume":"12 1","pages":"233 - 237"},"PeriodicalIF":0.0,"publicationDate":"2000-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87914040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alterations in Nitric Oxide Activity and Sensitivity in Early Streptozotocin-Induced Diabetes Depend on Arteriolar Size","authors":"B. vanDam, C. Demirci, H. Reitsma, A. V. van Lambalgen, G. C. van den Bos, G. Tangelder, C. Stehouwer","doi":"10.1155/EDR.2000.221","DOIUrl":"https://doi.org/10.1155/EDR.2000.221","url":null,"abstract":"Changes in NO activity may play an important role in the early increase in microvascular flow that has been implicated in the pathogenesis of diabetic microangiopathy. We assessed, in the in situ spinotrapezius muscle preparation of 6 weeks' streptozotocin-diabetic rats (n = 6) and of agematched controls (n = 8), basal inside diameters of A2–A4 arterioles and the reactivity to topically applied acetylcholine and nitroprusside, before and after NG-nitro-L-arginine. In diabetic rats, cholinergic vasodilatation in A2–A4 arterioles was intact. Basal diameter in A3 and A4 arterioles was significantly higher in streptozotocin-diabetic rats. The increased basal diameter in A3 arterioles was partially due to an increased contribution of NO to basal diameter. The response to nitroprusside was impaired in streptozotocin-diabetic rats in A2, but not in A3 and A4 arterioles. Thus, this study shows that NO activity and sensitivity are altered after 6 weeks of streptozotocin-induced diabetes. These streptozotocin-induced changes are anatomically specific and, for arterioles, depend on their position within the vascular tree.","PeriodicalId":14040,"journal":{"name":"International journal of experimental diabetes research","volume":"11631 1","pages":"221 - 232"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81323179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"D-glucose Stimulates the Na+/K+ Pump in Mouse Pancreatic Islet Cells","authors":"A. Elmi, L. Idahl, P. Sandström, J. Sehlin","doi":"10.1155/EDR.2000.155","DOIUrl":"https://doi.org/10.1155/EDR.2000.155","url":null,"abstract":"To determine the effect of D-glucose on the β-cell Na+/K+ pump, 86Rb+ influx was studied in isolated, -cell-rich islets of Umeå-ob/ob mice in the absence or presence of lmM ouabain. D-glucose (20 mM) stimulated the ouabain-sensitive portion of 86Rb+ influx by 65%, whereas the ouabain-resistant portion was inhibited by 48%. The Na+/K+ ATPase activity in homogenates of islets of Umeå-ob/ob mice or normal mice was determined to search for direct effects of D-glucose. Thus, ouabain-sensitive ATP hydrolysis in islet homogenates was measured in the presence of different D-glucose concentrations. No effect of D-glucose (3–20 mM) was observed in either ob/ob or normal islets at the optimal Na+/K+ ratio for the enzyme (135 mM Na+ and 20 mM K+). Neither D-glucose (3–20 mM) nor L-glucose or 3-O-methyl-D-glucose (20 mM) affected the enzyme activity at a high Na+/K+ ratio (175 mM Na+ and 0.7mM K+). Diphenylhydantoin (150 μM) decreased the enzyme activity at optimal Na+/K+ ratio, whereas 50 μM of the drug had no effect. The results suggest that D-glucose induces a net stimulation the Na+/K+ pump of β-cells in intact islets and that D-glucose does not exert any direct effect on the Na+/K+ ATPase activity.","PeriodicalId":14040,"journal":{"name":"International journal of experimental diabetes research","volume":"284 1","pages":"155 - 164"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86398116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Changes in the Growth Hormone-IGF-I Axis in Non-obese Diabetic Mice","authors":"D. Landau, Y. Segev, R. Eshet, A. Flyvbjerg, M. Phillip","doi":"10.1155/EDR.2000.9","DOIUrl":"https://doi.org/10.1155/EDR.2000.9","url":null,"abstract":"We investigated the changes in GH-IGF-I axis in non-obese diabetic (NOD)-mice, a model of insulin dependent diabetes mellitus. Diabetic female NOD mice and their age- and sex-matched controls were sacrificed at 4, 14, 21 and 30 days (30d DM) after the onset of glycosuria. Serum GH levels increased and serum IGF-I levels decreased in the 30d DM group (182 ± 32% and 45 ± 24% of age-matched controls respectively, p < 0.05). Another group (30d DM + I) was given SC insulin, and its serum IGF-I levels remained decreased. Liver GH receptor (GHR) and GH binding protein (GHBP) mRNA levels, as well as liver membrane GH binding assays were deeply decreased in the 30d DM group in comparison to controls. GHR message and binding capacity remained decreased in the 30d DM + I group. Renal GHR mRNA was decreased at 21d DM but not at 14d DM, whereas GHBP mRNA remained unchanged throughout the experiment. In conclusion, increased serum GH levels are documented in NOD diabetic mice, similarly to the changes described in humans. The decrease in GHR levels and decreased serum IGF-I in spite of increased circulating GH suggest a state of GH resistance.","PeriodicalId":14040,"journal":{"name":"International journal of experimental diabetes research","volume":"16 1","pages":"9 - 18"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84377288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstracts from The 8th International Workshop on Lessons from Animal Diabetes","authors":"P. Serup, J. Jensen, J. Hald, O. Madsen","doi":"10.1155/EDR.2001.251","DOIUrl":"https://doi.org/10.1155/EDR.2001.251","url":null,"abstract":"s of the 8th International Workshop on Lessons from Animal Diabetes Joint with The 15th Japan Association of Animal Diabetes Research TOKYO, JAPAN, JULY 24–26, 2001 Pancreatic Stem Cells and Islet Cell Differentiation PALLE SERUP, JAN JENSEN, JACOB HALD and OLE D. MADSEN Department of Developmental Biology, Hagedorn Research Institute, Gentofte, Denmark During the embryonic growth mechanisms that are not fully clear ensures that exoand endocrine cells are formed in the correct proportion. The embryonic endocrine progenitor cells are a subset of the developing Pdx1 pancreatic epithelial cells marked by the expression of Neurogenin3 (Ngn3). Ngn3 encodes a basic-Helix-Loop-Helix (bHLH) transcription factor (NGN3) that is required for the expression of NeuroD (as well as other transcription factor genes); moreover, ectopic Ngn3 expression can induce differentiation of embryonic pancreatic epithelium into α-cells at the expense of other pancreatic cell types. Notch signaling appears to control the activity of NGN3 and acts as a switch that determines the choice of the progenitor cells; the choice being to either remain as dividing precursor cells or to differentiate into endocrine cells. NGN3 is thought to activate transcription of the Notch ligand Dll–1. Once Dll–1 expression is induced in a differentiating cell it interacts with Notch, expressed on neighbouring cells. Notch activates a number of genes among which is the negatively acting bHLH gene Hes-1. This pathway (termed lateral inhibition) thus inhibits NGN3 activity and consequently endocrine differentiation and Dll–1 expression in the receiving cells. Lateral inhibition assures that only a few precursor cells differentiate and that a large fraction of the endocrine precursor cells in the pancreas are maintained in a dividing state until late stages of pancreatic development. In mice deficient for Notch pathway components, the precursor cells differentiate prematurely into endocrine cells. (Supported by NIH DK-55284) Molecular Pathogenesis of Type 2 Diabetes in Knockout Mice Models TAKASHI KADOWAKI, M.D., Ph.D. Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo Type 2 diabetes is a complex disease caused by interactions of multiple genes and environmental factors such as high-fat diet and sedentary life-style. Since type 2 diabetes is characterized by insulin resistance and relative insulin deficiency, we have tried to dissect molecular pathogenesis of type 2 diabetes by generating several knockout mice models with a lack of each key molecules of signalling pathways of either insulin action or insulin Int. Jnl. Experimental Diab. Res., Vol. 2, pp. 251–297 Copyright © 2001 Taylor & Francis, Inc. 1560-4284/01 $12.00 + .00","PeriodicalId":14040,"journal":{"name":"International journal of experimental diabetes research","volume":"36 1","pages":"251 - 297"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87273285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}