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建立普通狨猴 1 型糖尿病模型。

Establishment of a diabetes mellitus type 1 model in the common marmoset.

机构信息

Department of Pancreatic Islet Cell Transplantation, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan.

Department of Regenerative Medicine, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan.

出版信息

Sci Rep. 2019 Oct 10;9(1):14546. doi: 10.1038/s41598-019-51199-5.

Abstract

Common marmosets have attracted considerable attention as a small standard primate model in biomedical research. However, no marmoset diabetes model is available. Here, we established a marmoset diabetes model via the combination of partial pancreatectomy and intravenous streptozotocin (STZ). A partial pancreatectomy was performed in 11 common marmosets and multiple STZ doses were intravenously administered. Diabetes was diagnosed upon sustained hyperglycaemia (nonfasting blood glucose level >200 mg/dl). Blood glucose and biochemistry were periodically assessed, in addition to glucose tolerance testing, continual blood glucose determination using a continuous glucose monitoring system, urine testing and histological evaluation. In 8 of the 11 animals (73%), diabetes mellitus was induced. The diabetic marmosets also showed abnormal intravenous and oral glucose tolerance test results. Blood glucose levels decreased in response to human insulin administration. The hyperglycaemic state was irreversible and persisted for more than 3 months, and the animals' condition was manageable via daily insulin administration. Thus, diabetes can be successfully induced and maintained in the common marmoset via partial pancreatectomy and STZ administration. This protocol effectively generates a valuable animal model for studying disease pathogenesis, risk factors and therapeutic interventions, including islet transplantation.

摘要

普通狨猴作为一种小型标准灵长类动物模型,在生物医学研究中受到了广泛关注。然而,目前还没有狨猴糖尿病模型。在这里,我们通过部分胰腺切除术和静脉注射链脲佐菌素(STZ)联合建立了狨猴糖尿病模型。11 只普通狨猴接受了部分胰腺切除术,并静脉注射了多次 STZ。持续高血糖(非空腹血糖水平>200mg/dl)可诊断为糖尿病。除了葡萄糖耐量试验、连续血糖监测系统的连续血糖测定、尿液检测和组织学评估外,还定期评估血糖和生化指标。在 11 只动物中的 8 只(73%)中诱导出了糖尿病。糖尿病狨猴的静脉和口服葡萄糖耐量试验结果也异常。给予人胰岛素后,血糖水平下降。高血糖状态是不可逆的,持续时间超过 3 个月,通过每天给予胰岛素可使动物的病情得到控制。因此,通过部分胰腺切除术和 STZ 给药可以成功诱导和维持普通狨猴的糖尿病。该方案有效地生成了一种有价值的动物模型,可用于研究疾病发病机制、风险因素和治疗干预措施,包括胰岛移植。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd6d/6787219/279827cde996/41598_2019_51199_Fig1_HTML.jpg

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