Cappelli Ana Paula G, Zoppi Claudio C, Silveira Leonardo R, Batista Thiago M, Paula Flávia M, da Silva Priscilla M R, Rafacho Alex, Barbosa-Sampaio Helena C, Boschero Antonio C, Carneiro Everardo M
Department of Structural and Functional Biology, Cellular Biology and Physiology and Biophysics, Institute of Biology, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
Laboratory of Experimental Physiology, Department of Physiological Sciences, Federal University of Maranhão (UFMA), São Luís, Maranhão, Brazil.
J Cell Physiol. 2018 Jan;233(1):486-496. doi: 10.1002/jcp.25908. Epub 2017 May 3.
In the present study, we investigated the relationship between early life protein malnutrition-induced redox imbalance, and reduced glucose-stimulated insulin secretion. After weaning, male Wistar rats were submitted to a normal-protein-diet (17%-protein, NP) or to a low-protein-diet (6%-protein, LP) for 60 days. Pancreatic islets were isolated and hydrogen peroxide (H O ), oxidized (GSSG) and reduced (GSH) glutathione content, CuZn-superoxide dismutase (SOD1), glutathione peroxidase (GPx1) and catalase (CAT) gene expression, as well as enzymatic antioxidant activities were quantified. Islets that were pre-incubated with H O and/or N-acetylcysteine, were subsequently incubated with glucose for insulin secretion measurement. Protein malnutrition increased CAT mRNA content by 100%. LP group SOD1 and CAT activities were 50% increased and reduced, respectively. H O production was more than 50% increased whereas GSH/GSSG ratio was near 60% lower in LP group. Insulin secretion was, in most conditions, approximately 50% lower in LP rat islets. When islets were pre-incubated with H O (100 μM), and incubated with glucose (33 mM), LP rats showed significant decrease of insulin secretion. This effect was attenuated when LP islets were exposed to N-acetylcysteine.
在本研究中，我们调查了早期蛋白质营养不良诱导的氧化还原失衡与葡萄糖刺激的胰岛素分泌减少之间的关系。断奶后，将雄性Wistar大鼠分为正常蛋白质饮食组（17%蛋白质，NP）或低蛋白质饮食组（6%蛋白质，LP），持续60天。分离胰岛并定量过氧化氢（H₂O₂）、氧化型（GSSG）和还原型（GSH）谷胱甘肽含量、铜锌超氧化物歧化酶（SOD1）、谷胱甘肽过氧化物酶（GPx1）和过氧化氢酶（CAT）基因表达以及酶促抗氧化活性。预先用H₂O₂和/或N-乙酰半胱氨酸孵育的胰岛，随后用葡萄糖孵育以测量胰岛素分泌。蛋白质营养不良使CAT mRNA含量增加了100%。LP组SOD1和CAT活性分别增加了50%和降低了。LP组H₂O₂产生增加了50%以上，而GSH/GSSG比值降低了近60%。在大多数情况下，LP大鼠胰岛的胰岛素分泌降低了约50%。当胰岛预先用H₂O₂（100μM）孵育，然后用葡萄糖（33mM）孵育时，LP大鼠的胰岛素分泌显著下降。当LP胰岛暴露于N-乙酰半胱氨酸时，这种作用减弱。
