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在清醒且无压力的食蟹猴中使用植入式遥测装置进行长期血糖监测。

Long-term blood glucose monitoring with implanted telemetry device in conscious and stress-free cynomolgus monkeys.

机构信息

Crown Bioscience, Inc., Taicang, Jiangsu Province, The People's Republic of China.

Data Sciences International, St. Paul, MN, USA.

出版信息

J Endocrinol Invest. 2017 Sep;40(9):967-977. doi: 10.1007/s40618-017-0651-9. Epub 2017 Apr 1.

Abstract

AIMS

Continuous blood glucose monitoring, especially long-term and remote, in diabetic patients or research is very challenging. Nonhuman primate (NHP) is an excellent model for metabolic research, because NHPs can naturally develop Type 2 diabetes mellitus (T2DM) similarly to humans. This study was to investigate blood glucose changes in conscious, moving-free cynomolgus monkeys (Macaca fascicularis) during circadian, meal, stress and drug exposure.

MATERIALS AND METHODS

Blood glucose, body temperature and physical activities were continuously and simultaneously recorded by implanted HD-XG telemetry device for up to 10 weeks.

RESULTS AND DISCUSSION

Blood glucose circadian changes in normoglycemic monkeys significantly differed from that in diabetic animals. Postprandial glucose increase was more obvious after afternoon feeding. Moving a monkey from its housing cage to monkey chair increased blood glucose by 30% in both normoglycemic and diabetic monkeys. Such increase in blood glucose declined to the pre-procedure level in 30 min in normoglycemic animals and >2 h in diabetic monkeys. Oral gavage procedure alone caused hyperglycemia in both normoglycemic and diabetic monkeys. Intravenous injection with the stress hormones, angiotensin II (2 μg/kg) or norepinephrine (0.4 μg/kg), also increased blood glucose level by 30%. The glucose levels measured by the telemetry system correlated significantly well with glucometer readings during glucose tolerance tests (ivGTT or oGTT), insulin tolerance test (ITT), graded glucose infusion (GGI) and clamp.

CONCLUSION

Our data demonstrate that the real-time telemetry method is reliable for monitoring blood glucose remotely and continuously in conscious, stress-free, and moving-free NHPs with the advantages highly valuable to diabetes research and drug discovery.

摘要

目的

在糖尿病患者或研究中,连续的血糖监测,尤其是长期的、远程的血糖监测,极具挑战性。非人类灵长类动物(NHP)是代谢研究的极佳模型,因为 NHP 可以像人类一样自然地发展为 2 型糖尿病(T2DM)。本研究旨在调查清醒、无束缚的食蟹猴(Macaca fascicularis)在昼夜节律、进餐、应激和药物暴露期间的血糖变化。

材料和方法

通过植入的 HD-XG 遥测设备,连续、同步地记录血糖、体温和身体活动,最长可达 10 周。

结果与讨论

正常血糖猴子的血糖昼夜变化与糖尿病动物明显不同。下午进食后餐后血糖升高更为明显。将猴子从饲养笼中转移到猴椅上,会使正常血糖和糖尿病猴子的血糖分别升高 30%。在正常血糖动物中,血糖升高在 30 分钟内降至术前水平,而在糖尿病猴子中则需要>2 小时。口服灌胃程序本身会导致正常血糖和糖尿病猴子的高血糖。静脉注射应激激素血管紧张素 II(2μg/kg)或去甲肾上腺素(0.4μg/kg)也会使血糖水平升高 30%。遥测系统测量的血糖水平与葡萄糖耐量试验(ivGTT 或 oGTT)、胰岛素耐量试验(ITT)、分级葡萄糖输注(GGI)和钳夹期间的血糖仪读数具有显著相关性。

结论

我们的数据表明,实时遥测方法可靠,可用于监测清醒、无应激、无束缚的 NHP 中血糖的远程和连续变化,这对糖尿病研究和药物发现具有重要价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af5b/5559582/f97327bece45/40618_2017_651_Fig1_HTML.jpg

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