Wos İndeksli Yayınlar Koleksiyonu
Permanent URI for this collectionhttps://hdl.handle.net/11727/4807
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Item Beta-Cell Golgi Stress Response to Lipotoxicity and Glucolipotoxicity: A Preliminary Study of a Potential Mechanism of Beta-Cell Failure in Posttransplant Diabetes and Intraportal Islet Transplant(2022) Tutuncu, Neslihan Bascil; Verdi, Hasibe; Yalcin, Yaprak; Cebi, Pinar Baysan; Kinik, Sibel; Tutuncu, Tanju; Atac, Fatma Belgin; 0000-0002-1816-3903; 0000-0002-9337-9106; 0000-0002-9141-9987; 35791832; ABG-5027-2020; ABB-4078-2020Objectives: Lipotoxicity and glucolipotoxicity are among the most important triggers of beta-cell failure in patients with type 2 and posttransplant diabetes. Because the Golgi apparatus is a vital organelle in secretory cells like beta cells, its behavior under stress conditions determines the cell's functional capacity.Materials and Methods: To mimic lipotoxicity and glucolipotoxicity as metabolic stresses for beta-cell failure, rat insulinoma INS-1E cells were treated with palmitic acid, glucose, or both. Cells were cultured in the presence of 5.0, 16.7, or 33 mM glucose with or without 0.5 mM palmitic acid for 8, 16, 24, and 48 hours. Incubation in the presence of any of the 3 concentrations of glucose with 0.5 mM palmitic acid provided glucolipotoxicity. In addition to the endop-lasmic reticulum stress marker (Hspa5), we evaluated changes in Golgi function under experimental metabolic stresses. In doing this, we measured expression levels of the genes coding Golgi structural proteins (Acbd3, Golga2, and Arf1), Golgi glycosylation enzymes sialyltransferaz10 and sialyltransferase 1 (St3gal1), and Golgi stress mediators (Creb3 and Arf4).Results: Golgi responded to lipotoxicity and glucolipotoxicity by increasing the expression of St3gal1 (P = .05 in both conditions) and Creb3 (P = .022 and P = .01, respectively). The Arf4 gene transcript also increased in glucolipotoxic media (P = .03). Glucotoxicity alone did not induce a change in the transcript levels of Creb3 and Arf4. Lipotoxicity and glucolipotoxicity induced Creb3 and Arf4 expression, which are important Golgi stress response mediators leading to apoptosis.Conclusions: This preliminary study showed that the Golgi stress response is important in lipotoxic and glucolipotoxic conditions in terms of beta-cell failure. Solving the mystery of intracellular molecular mechanisms leading to beta-cell dysfunction is crucial to understanding the pathophysiology of posttrans-plant diabetes and most probably the failure of intraportal islet transplants in the long term.Item beta-3AR W64R Polymorphism and 30-Minute Post-Challenge Plasma Glucose Levels in Obese Children(2015) Verdi, Hasibe; Kinik, Sibel Tulgar; Yalcin, Yaprak Yilmaz; Sahin, Nursel Muratoglu; Yazici, Ayse Canan; Atac, F.Belgin; 25800470Objective: In this study, we aimed to investigate the association of W64R polymorphism of the beta 3-adrenergic receptor gene (beta-3AR) with childhood obesity and related pathologies. Methods: beta-3AR gene W64R genotyping was carried out in 251 children aged 6-18 years. Of these subjects, 130 were obese (62 boys) and 121 were normal-weight (53 boys). In the obese group, fasting lipids, glucose and insulin levels were measured. Oral glucose tolerance test (OGTT) was performed in 75 of the obese patients. Results: The frequency of W64R genotype was similar in obese and nonobese children. In obese children, relative body mass index, waist-to-hip ratio, serum lipid, glucose and insulin levels, as well as homeostasis model assessment of insulin resistance (HOMA-IR) scores were not different between Arg allele carriers (W64R and R64R) and noncarriers (W64W). In 75 obese children, OGTT results showed that Arg allele carriers had significantly higher 30-minute glucose levels (p=0.027). Conclusion: W64R polymorphism of the beta-3AR gene is not associated with obesity and waist-to-hip ratio in Turkish children. Although there were no relationships between the genotypes and lipid, glucose/insulin levels or HOMA-IR, the presence of W64R variant seemed to have an unfavorable influence on early glucose excursion after glucose loading.