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首页> 外文期刊>Journal of pharmacology & toxicology. >Pancreatic Gene Expression Altered Following Dietary Exposure to 2-Aminoanthracene: Links to Diabetogenic Activity
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Pancreatic Gene Expression Altered Following Dietary Exposure to 2-Aminoanthracene: Links to Diabetogenic Activity

机译：饮食中2-氨基蒽的饮食后胰腺基因表达改变：链接到糖尿病的活动。

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The mutagen 2-aminoanthracene (2-AA) is an aromatic amine or arylamine, which belongs to a class of polycyclic aromatic hydrocarbons. 2-AA is used in the manufacturing of a wide variety of chemicals, drugs, dyes and polymers. Non-occupational sources include tobacco smoking and cooked foods. The goal of this study is to evaluate pancreatic gene expression patterns in Fischer-344 (F-344) male rats exposed to 2-AA. As a first step the effects of 2-aminoanthracene exposure on the pancreas with particular interest in genes that relate to insulin and insulin metabolism. To achieve this goal, twenty-four post-weaning, 3-4 week old F-344 male rats were exposed to 0 mg kg~-1-diet (control), 50 mg kg~-1-diet (low dose), 75 mg kg~-1-diet (medium dose) and 100 mg kg~-1-diet (high dose) 2-AA for 14 and 28 days followed by analysis of the pancreas for broad gene expression changes. Results obtained from our study suggest most of the mRNA transcripts that were differentially expressed are involved in energy metabolism in the pancreas, protein digestion and some that play an active role in pancreatitis and pancreatic cancer. Some of these genes include: insulin, colipase pancreatic, carboxypeptidase, chymotrypsinogen Bl and chymotrypsin C (caldecrin). These findings seem to point to the role of 2-AA in the dysregulation of several pancreatic genes that regulate lipid and protein metabolism in a way that involves a feedback mechanism which may ultimately lead to insulin resistance and tissue autolysis. Quantitative PCR determination of fold changes in selected genes show similar trends to global expression determined via microarray analyses.
机译：诱变剂2-氨基蒽（2-AA）是芳族胺或芳基胺，属于多环芳族烃的一类。 2-AA用于制造多种化学品，药物，染料和聚合物。非职业来源包括吸烟和熟食。这项研究的目的是评估暴露于2-AA的Fischer-344（F-344）雄性大鼠的胰腺基因表达模式。第一步，对2-氨基蒽的暴露对胰腺的影响尤其是与胰岛素和胰岛素代谢有关的基因受到关注。为了实现这一目标，将24只断奶后3-4周大的F-344雄性大鼠暴露于0 mg kg-1饮食（对照），50 mg kg-1饮食（低剂量）， 75 mg kg-1饮食（中等剂量）和100 mg kg-1饮食（高剂量）2-AA，持续14天和28天，然后分析胰腺的广泛基因表达变化。从我们的研究中获得的结果表明，差异表达的大多数mRNA转录物都参与胰腺的能量代谢，蛋白质消化，并且其中一些在胰腺炎和胰腺癌中起积极作用。这些基因中的一些包括：胰岛素，胰酶，胰蛋白酶，羧肽酶，胰凝乳蛋白酶原B1和胰凝乳蛋白酶C（钙调蛋白）。这些发现似乎表明2-AA在几种胰腺基因失调中的作用，这些胰腺基因以一种涉及反馈机制的方式调节脂质和蛋白质的代谢，最终可能导致胰岛素抵抗和组织自溶。所选基因倍数变化的定量PCR测定显示与通过微阵列分析确定的整体表达相似的趋势。

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