Wei Yang , Si-Cong Si , Hong-Yu Luo, Yi-Xin Ma, Huan Zhao
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引用次数: 0
Abstract
Objective
Effective methods for establishing an aged animal model of diabetes and glycemic fluctuation have rarely been investigated. The aim of the study was to explore the feasibility of inducing glycemic fluctuation in aged Sprague–Dawley rats and to evaluate the corresponding changes in cognitive function.
Methods
Male rats aged 48 weeks were fed a high-fat and high-glucose diet and given streptozotocin intraperitoneally to establish a rat model of type 2 diabetes mellitus (T2DM). Then, glycemic fluctuation was induced via three different protocols: (1) intraperitoneal injection of glucose; (2) sequential fasting, insulin injection, and normal diet; and (3) intermittent intraperitoneal injections of glucose and insulin.
Results
All three protocols were effective at inducing glycemic fluctuation in aged rats with T2DM, with successful modeling rates of 60 %, 90 %, and 70 %, respectively. Aged T2DM rats with glycemic fluctuation showed significant increases in glycemic variability compared with controls, including in the mean blood glucose, postprandial glycemic excursion, largest amplitude of glycemic excursion, and standard deviation of blood glucose values (all P < 0.05). Additionally, rats with glycemic fluctuation had more severe insulin resistance and dyslipidemia (P < 0.05). Morris water maze testing showed a trend of longer escape latency in the navigation test for rats in the glycemic fluctuation groups, suggesting impaired cognitive function. Pathological analysis showed degenerative changes in the CA1 hippocampal region of rats in the glycemic fluctuation groups. Finally, differential gene expression analysis revealed 1323 significantly altered genes in the GV group, with 691 upregulated and 632 downregulated. The dysregulated genes were predominantly associated with the axon guidance pathway and potassium channel regulation.
Conclusions
The proposed protocols were effective at establishing an aged T2DM rat model with glycemic fluctuation, and rats with glycemic fluctuation exhibited diminished cognitive function.
期刊介绍：
An international multidisciplinary journal devoted to fundamental research in the brain sciences.
Brain Research publishes papers reporting interdisciplinary investigations of nervous system structure and function that are of general interest to the international community of neuroscientists. As is evident from the journals name, its scope is broad, ranging from cellular and molecular studies through systems neuroscience, cognition and disease. Invited reviews are also published; suggestions for and inquiries about potential reviews are welcomed.
With the appearance of the final issue of the 2011 subscription, Vol. 67/1-2 (24 June 2011), Brain Research Reviews has ceased publication as a distinct journal separate from Brain Research. Review articles accepted for Brain Research are now published in that journal.
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