Original Data

Rev Diabet Stud, 2005, 2(3):136-145 DOI 10.1900/RDS.2005.2.136

High-Fat Feeding During Gestation and Nursing Period have Differential Effects on the Insulin Secretory Capacity in Offspring from Normal Wistar Rats

Stig E.U. Dyrskog, Søren Gregersen, Kjeld Hermansen

Department of Endocrinology and Metabolism C, Aarhus Sygehus THG, Aarhus University Hospital, Tage-Hansens Gade 2, 8000 Aarhus C, Denmark.
Address correspondence to: Stig E.U. Dyrskog, e-mail: stig.dyrskog@ki.au.dk.

Abstract

Restriction of protein or energy intake during gestation or early life is linked to developmental defects in the endocrine pancreas and insulin resistance. AIMS: To study whether a saturated fatty acid-rich diet during gestation and/or after the weaning period may be detrimental to the insulin secretory capacity later in life. STUDY DESIGN: Female Wistar rats were fed diets rich in carbohydrate (CHO) or saturated fat (SAFA) during pregnancy. The male offspring were split into five subgroups: after birth group 1 (control) continued on CHO and group 3 on SAFA. Group 2 continued on the CHO diet during the nursing period but changed to SAFA post weaning. Group 4 continued on SAFA, but changed to CHO post weaning. For group 5 the offspring of mothers given a SAFA diet were changed to nursing mothers on a CHO diet immediately after birth, and continued on the same diet post weaning. After 14 wk, the islets of Langerhans were isolated for determination of insulin secretory capacity in static incubation and dynamic perifusion experiments. RESULTS: We found a negative correlation (Coef: -3.1, 95% CI: -6.1 to -0.0, p < 0.05) between a diet rich in saturated fat fed to mothers during gestation and a positive correlation (Coef: 4.4, 95% CI: 0.9 to 7.8, p = 0.01) between nursing mothers’ diet and the capability to secrete insulin in the offspring. CONCLUSION: Our results indicate the importance of applying a nutrient-balanced diet during pregnancy and the nursing period on the later insulin secretory capacity in the offspring.

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Rev Diabet Stud, 2005, 2(3):146-156 DOI 10.1900/RDS.2005.2.146

Insulinotropic and Anti-Inflammatory Effects of Rosiglitazone in Experimental Autoimmune Diabetes

Wageh M. Awara1, Alaa E. El-Sisi1, Mohamed El-Refaei2, Mona M. El-Naa1, Karima El-Desoky3

1Department of Pharmacology/Toxicology, College of Pharmacy, University of Tanta, Egypt.
2Department of Biochemistry, Genetic Engineering and Biotechnology Research Institute, Minofia University, Egypt.
3Department of Pathology, Faculty of Medicine, University of Tanta, Egypt.
Address correspondence to: Wageh M. Awara, e-mail: wagawara@yahoo.com.

Abstract

Cytokines and nitric oxide (NO) are involved in the pathogenesis of autoimmune diabetes mellitus (DM). Rosiglitazone is an insulin-sensitizing drug that is a ligand for the nuclear receptor peroxisome proliferator-activated receptor-gamma (PPAR-γ). The anti-inflammatory and immunomodulating properties of PPAR-γ have been documented. The aim of this study is to investigate the effectiveness of rosiglitazone in autoimmune DM and to clarify the possible mechanism(s) involved. Autoimmune DM was induced in adult male Balb/c mice by co-administration of cyclosporin A and multiple low doses of streptozotocin. Diabetic mice were treated daily with rosiglitazone (7 mg/kg, p.o.) for 21 days. Blood glucose level (BGL), serum insulin level and pancreatic levels of tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ) and NO were measured. Histopathological examination and immunohistochemical determination of CD4 and CD8 T lymphocytes in the pancreatic islets were performed. In addition, analysis of pancreatic protein expression was carried out. The results showed that rosiglitazone treatment resulted in a significant decrease in the BGL and the pancreatic levels of TNF-α, IFN-γ and NO compared to diabetic mice. The serum insulin level was significantly increased after rosiglitazone treatment compared to diabetic mice. The destroyed pancreatic islets were regenerated and became free from both CD4 and CD8 T cells after treatment. Furthermore, many changes in pancreatic protein expression were observed. These results suggest that rosiglitazone has a beneficial effect in the treatment of autoimmune diabetes, an effect that seemed to be a secondary consequence of its anti-inflammatory and immunomodulating properties and might be reflected at the level of protein expression.

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Rev Diabet Stud, 2005, 2(3):157-164 DOI 10.1900/RDS.2005.2.157

Association of Postprandial Hyperglycemia with in Vitro LDL Oxidation in Non-Smoking Patients with Type 1 Diabetes - a Cross-Sectional Study

Simone H. de Castro1, Hugo C. Castro-Faria-Neto2, Marilia B. Gomes1

1Department of Medicine, Diabetes Unit, State University Hospital of Rio de Janeiro, Brazil.
2Department Immunopharmacology Laboratory, Department of Physiology and Pharmacodynamics, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Brazil.
Address correspondence to: Marilia B. Gomes, e-mail: mariliabgomes@uol.com.br.

Abstract

BACKGROUND: Cardiovascular disease is the main cause of death in patients with type 1 diabetes. Since oxidized low density lipoprotein (LDL) is considered to be a critical factor in the atherosclerotic process, the aim of our study was to assess the influence of different parameters of glycemic control on susceptibility to oxidative stress from low density lipoprotein (LDL) in patients with type 1 diabetes without microvascular or macrovascular complications. METHODS: Forty patients and 33 non-diabetic individuals matched for gender, age and body mass index (BMI) were evaluated. The two groups underwent determination of lipid profile, fasting and postprandial glucose control and measurement of glycated hemoglobin (HbA1c). Spectrophotometric analysis of the LDL oxidation index was performed before and 1, 3, 6 and 24 h after the addition of copper sulfate to purified LDL fractions. RESULTS: The oxidation coefficient for LDL presented similar basal values in the two groups; however, at 3 h, LDL showed a higher degree of oxidation in patients with type 1 diabetes. Correlations with the metabolic control variables were significant only for postprandial glycemia. Stepwise multiple regression showed that post-prandial glycemia and sex were the significant independent variables. CONCLUSION: LDL from patients with type 1 diabetes showed high susceptibility to oxidative stress and this susceptibility was markedly related to the postprandial glucose levels. The influence of our findings on the development of chronic complications in patients with type 1 diabetes must be addressed in prospective studies.

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