Biochemical and histological effects of exendin-4 (exenatide) on the rat pancreas
Biochemical and histological effects of exendin-4 (exenatide) on the rat pancreas
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DOI：
10.1007/s00125-009-1515-4
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发表时间：
2010-01-01
期刊：
影响因子：
8.2
通讯作者：
Alba, L. M.
中科院分区：
文献类型：
--
作者：
Nachnani, J. S.;Bulchandani, D. G.;Alba, L. M.
Exendin-4是一种由39个氨基酸组成的胰高血糖素样肽受体激动剂，已被批准用于治疗2型糖尿病。许多报告描述，接受 Exendin-4（艾塞那肽）治疗的人类急性胰腺炎发病率有所增加。先前的研究评估了 exendin-4 对 β 细胞和 β 细胞功能的影响。我们评估了exendin-4对大鼠胰腺的组织学和生化作用。我们研究了20只Sprague-Dawley雄性大鼠，其中10只用exendin-4治疗，另外10只用作对照。研究期限为75天。取出血清和胰腺组织用于生化和组织学研究。比较两组之间的血糖、淀粉酶、脂肪酶、胰岛素和脂肪细胞因子。Exendin-4处理的动物与对照大鼠相比，胰腺腺泡炎症更多，核固缩更多，体重明显减轻。他们的血清脂肪酶也比对照动物更高。与未治疗的对照组相比，Exendin-4 治疗与较低的胰岛素和瘦素水平以及较低的 HOMA 值相关。尽管与对照组动物相比，在大鼠中使用 Exendin-4 与体重增加减少、胰岛素抵抗降低和瘦素水平降低相关，但在大鼠中长期使用 Exendin-4 会导致胰腺腺泡炎症和固缩。这引起了人们对接受肠促胰岛素模拟疗法的人诱发急性胰腺炎的可能性的严重担忧。
Exendin-4 is a 39 amino acid agonist of the glucagon-like peptide receptor and has been approved for treatment of type 2 diabetes. Many reports describe an increased incidence of acute pancreatitis in humans treated with exendin-4 (exenatide). Previous studies have evaluated the effect of exendin-4 on beta cells and beta cell function. We evaluated the histological and biochemical effects of exendin-4 on the pancreas in rats.We studied 20 Sprague-Dawley male rats, ten of which were treated with exendin-4 and ten of which were used as controls. The study period was 75 days. Serum and pancreatic tissue were removed for biochemical and histological study. Blood glucose, amylase, lipase, insulin and adipocytokines were compared between the two groups.Animals treated with exendin-4 had more pancreatic acinar inflammation, more pyknotic nuclei and weighed significantly less than control rats. They also had higher serum lipase than control animals. Exendin-4 treatment was associated with lower insulin and leptin levels as well as lower HOMA values than in the untreated control group.Although the use of exendin-4 in rats is associated with decreased weight gain, lower insulin resistance and lower leptin levels than in control animals, extended use of exendin-4 in rats leads to pancreatic acinar inflammation and pyknosis. This raises important concerns about the likelihood of inducing acute pancreatitis in humans receiving incretin mimetic therapy.