胰岛素增敏剂 KBP-336 可预防糖尿病诱导的 ZDF 大鼠认知能力下降

IF 4.3 Q2 BUSINESS
Anna Thorsø Larsen, K. E. Mohamed, E. A. Petersen, M. A. Karsdal, K. Henriksen
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引用次数: 0

摘要

背景和目的糖尿病尤其是胰岛素抵抗与认知功能障碍的发病风险增加有关,因此抗糖尿病药物成为治疗神经退行性疾病的一种有趣的治疗选择。双淀粉样蛋白和降钙素受体激动剂(DACRAs)可对血糖控制和胰岛素敏感性产生有益影响。设计与干预用 DACRA KBP-336(4.5 nmol/kg Q3D)、淀粉样蛋白类似物 AM1213(25 nmol/kg QD)或药物治疗扎克糖尿病肥胖大鼠 18 周。此外,还评估了 KBP-336 后期干预的疗效,其中包括从第 30 天开始治疗的一组。结果在评估空间学习能力时,在整个研究期间接受 KBP-336 治疗的大鼠的表现明显优于 AM1213、药物和后期干预的 KBP-336。与车辆相比,KBP-336 和 AM1213 治疗都能改善空间记忆。结论综上所述,DACRA KBP-336 可改善糖尿病诱导的糖尿病大鼠空间学习和记忆损伤。此外,KBP-336 改善长期血糖控制的效果优于淀粉样蛋白类似物 AM1213。综上所述,KBP-336 因其抗糖尿病和胰岛素增敏特性,有望成为治疗认知障碍的候选药物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

The Insulin Sensitizer KBP-336 Prevents Diabetes-Induced Cognitive decline in ZDF Rats

The Insulin Sensitizer KBP-336 Prevents Diabetes-Induced Cognitive decline in ZDF Rats

Background and Objectives

Diabetes and especially insulin resistance are associated with an increased risk of developing cognitive dysfunction, making anti-diabetic drugs an interesting therapeutic option for the treatment of neurodegenerative disorders. Dual amylin and calcitonin receptor agonists (DACRAs) elicit beneficial effects on glycemic control and insulin sensitivity. However, whether DACRAs affect cognition is unknown.

Design and Intervention

Zucker Diabetic Fatty rats were treated with either the DACRA KBP-336 (4.5 nmol/kg Q3D), the amylin analog AM1213 (25 nmol/kg QD), or vehicle for 18 weeks. Further, the efficacy of a late KBP-336 intervention was evaluated by including a group starting treatment on day 30. Glucose control and tolerance were evaluated throughout the study and spatial learning and memory were evaluated by Morris Water Maze after 17 weeks of treatment.

Results

When evaluating spatial learning, rats receiving KBP-336 throughout the study performed significantly better than AM1213, vehicle, and late intervention KBP-336. Both KBP-336 and AM1213 treatments improved spatial memory compared to the vehicle. The overall performance in the cognitive tests was reflected in the treatment efficacy on glycemic control, where KBP-336 was superior to AM1213.

Conclusion

In summary, the DACRA KBP-336 ameliorates diabetes-induced spatial learning and memory impairment in diabetic rats. Further, KBP-336 improves long-term glycemic control superior to the amylin analog AM1213. Taken together, KBP-336 is, due to its anti-diabetic and insulin-sensitizing properties, a promising candidate for the treatment of cognitive impairments.

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来源期刊
The Journal of Prevention of Alzheimer's Disease
The Journal of Prevention of Alzheimer's Disease Medicine-Psychiatry and Mental Health
CiteScore
9.20
自引率
0.00%
发文量
0
期刊介绍: The JPAD Journal of Prevention of Alzheimer’Disease will publish reviews, original research articles and short reports to improve our knowledge in the field of Alzheimer prevention including: neurosciences, biomarkers, imaging, epidemiology, public health, physical cognitive exercise, nutrition, risk and protective factors, drug development, trials design, and heath economic outcomes.JPAD will publish also the meeting abstracts from Clinical Trial on Alzheimer Disease (CTAD) and will be distributed both in paper and online version worldwide.We hope that JPAD with your contribution will play a role in the development of Alzheimer prevention.
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