Original Data
| Rev Diabet Stud,
2005,
2(2):70-74 |
DOI 10.1900/RDS.2005.2.70 |
Manganese Superoxide Dismutase Alanine to Valine Polymorphism and Risk of Neuropathy and Nephropathy in Egyptian Type 1 Diabetic Patients
Tarek M. El Masry1, Mona A. M. Abou Zahra1, Mohammed M. El Tawil2, Rawhia A. Khalifa3
1Department of Clinical Pathology, Ain Shams University Hospital, Cairo, Egypt.
2Department of Pediatrics, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
3Department of Clinical Pathology, Research Institute of Ophthalmology.
Address correspondence to: Tarek M. El Masry, e-mail: tarek_msry@yahoo.com.
Abstract
Oxidative stress, characterized by a marked increase in the level of oxygen free radicals (OFR), has been implicated in the development of diabetic microangiopathic complications, such as diabetic neuropathy (DN) and nephropathy (DP). Antioxidant enzymes may protect against the rapid onset and progression of microangiopathy, by reducing the excess of OFR and peroxides. Mutations and polymorphisms in genes encoding such enzymes may therefore result in a predisposition to this disorder. AIM: we investigated the role of genes encoding the antioxidant enzyme, mitochondrial superoxide dismutase (Mn-SOD2), in DN and DP pathogenesis in an Egyptian population. We studied Ala(-9)Val polymorphism of the Mn-SOD2 gene in type 1 diabetic patients (n = 65) with DN (n = 40) or DP (n = 45). METHODS: we used polymerase chain reaction (PCR) assays with restriction fragment length polymorphism for rapid detection of polymorphisms. These assays involved the use of mismatch PCR primers to create restriction sites in the amplified product only in presence of the polymorphic base. The PCR product was then digested with AgeI restriction enzyme to detect Ala(-9)Val polymorphic sites. RESULTS: the frequencies of the Ala allele (odds ratio (OR) = 0.438, 95% CI of 0.247 - 0.778) and the Ala/Ala genotype (OR = 0.26, 95% CI of 1.39 - 10.266) were significantly lower in diabetic neuropathy patients. In contrast, the frequencies of the Val allele (OR = 2.282, 95% CI of 1.286 - 4.05) and the homozygous Val/Val genotype (OR = 6.68, 95% CI of 0.3 - 0.76) were significantly higher in patients with DN than diabetics without neuropathy. Although the Val allele was more frequently detected in DP patients than diabetics without nephropathy (OR = 3.2), this difference was statistically non-significant. In conclusion, Ala(-9)Val substitution in the Mn-SOD2 gene was associated with DN in Egyptian diabetic children but not a significant factor in diabetic patients with nephropathy.
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| Rev Diabet Stud,
2005,
2(2):75-83 |
DOI 10.1900/RDS.2005.2.75 |
Increased Transcriptional Preproinsulin II β-Cell Activity in Neonatal Nonobese Diabetic Mice: In Situ Hybridization Analysis
Marc Throsby1, Josiane Coulaud2, Sylvie Durant3, Francoise Homo-Delarche2
1Crucell Holland B.V., Leiden 2301 CA, The Netherlands.
2CNRS UMR 7059, Paris 7 University, 75005 Paris, France.
3INSERM U530, Centre Universitaire-UFR Biomédicale, 75006 Paris, France.
Address correspondence to: Francoise Homo-Delarche, e-mail: francoise.homo-delarche@paris7.jussieu.fr.
Abstract
In the prediabetic nonobese diabetic (NOD) mouse, a spontaneous model of type 1 diabetes, we previously reported transient postweaning hyperinsulinemia followed by progressive islet hyperplasia. A modified in situ hybridization technique was used to determine whether these effects were accompanied by changes in insulin transcriptional activity as a function of age. We found that NOD neonates express higher levels of preproinsulin II primary transcripts than age-matched C57BL/6 mice, but this difference disappeared within the first wk of age. To manipulate insulin transcriptional activity in NOD neonates, NOD mothers were treated with insulin during the last two wk of gestation. A down-regulation of β-cell hyperactivity was observed in female NOD neonates but not in male neonates. By contrast, the same insulin treatment applied to NODscid (severe combined immunodeficiency) mothers, devoid of functional lymphocytes but showing like NOD mice postweaning hyperinsulinemia, increased transcriptional β-cell activity in both sexes of neonates. In conclusion, NOD mice exhibit successive and transient signs of β-cell hyperactivity, reflected as early as birth by high transcriptional preproinsulin II activity and later, from weaning to around 10 wk of age, by hyperinsulinemia. Of note, when thinking in terms of in utero disease programming, the NOD neonatal transcriptional β-cell hyperactivity could be modulated by environmental (maternal and/or fetal) factors.
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| Rev Diabet Stud,
2005,
2(2):84-91 |
DOI 10.1900/RDS.2005.2.84 |
The Diterpene Glycoside, Rebaudioside A, Does not Improve Glycemic Control or Affect Blood Pressure After Eight Weeks Treatment in the Goto-Kakizaki Rat
Stig E.U. Dyrskog1, Per B. Jeppesen1, Jianguo Chen1, Lars P. Christensen2, Kjeld Hermansen1
1Department of Endocrinology and Metabolism C, Aarhus Sygehus THG, Aarhus University Hospital, Tage-Hansens Gade 2, 8000 Aarhus C, Denmark.
2Department of Food Science, Danish Institute of Agricultural Sciences, Research Centre Aarslev, Kirstinebjergvej 10, DK-5792 Aarslev, Denmark.
Address correspondence to: Stig E.U. Dyrskog, e-mail: stig.dyrskog@ki.au.dk.
Abstract
The plant, Stevia rebaudiana Bertoni (SrB), has been used for the treatment of diabetes in traditional medicine. Previously, we have demonstrated that long-term administration of the glycoside stevioside has insulinotropic, glucagonostatic, anti-hyperglycemic and blood pressure-lowering effects in type 2 diabetic animal models. The aim of this study was to elucidate if long-term administration of rebaudioside A, another glycoside isolated from the plant SrB, could improve glycemic control and lower blood pressure in an animal model of type 2 diabetes. We divided male Goto-Kakizaki (GK) rats into two groups which were fed a standard laboratory chow diet for eight weeks. The diet was supplemented with oral rebaudioside A (0.025 g/kg BW/day) in the experimental group. Blood glucose, weight, blood pressure and food intake were measured weekly. Animals were equipped with an intra-arterial catheter, and at week eight the conscious rats underwent an intra-arterial glucose tolerance test (IAGTT) (2.0 g/kg BW). During the IAGTT, the level of glucose, glucagon, and insulin responses did not differ significantly between the two groups. Fasting levels of glucose, glucagon, insulin or levels of blood lipids did not differ between the groups throughout the study period. We observed no effect on blood pressure or weight development. In conclusion, oral supplementation with rebaudioside A (0.025 g/kg BW/day) for eight weeks did not influence blood pressure or glycemic control in GK rats. Rebaudioside A failed to show the beneficial effects in diabetic animals previously demonstrated for stevioside.
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