McNay Ewan C, Sherwin Robert S
Department of Internal Medicine, Section of Endocrinology, Yale School of Medicine, New Haven, Connecticut, USA.
Diabetes. 2004 Feb;53(2):418-25. doi: 10.2337/diabetes.53.2.418.
The effects of recurrent hypoglycemia (RH) on cognition in human subjects remain controversial, perhaps in part due to difficulty in completely controlling previous hypoglycemic history. We used a model of RH in nondiabetic and diabetic rats to examine the effects of short-term (3 h daily for 3 days) RH on subsequent hippocampally dependent spatial memory, tested either at euglycemia or under acute hypoglycemia. Hippocampal metabolism was simultaneously measured using microdialysis. Antecedent RH improved task performance (79 +/- 2% alternation in nondiabetic RH animals vs. 63 +/- 3% in controls; P < 0.001) at euglycemia, accompanied by reversal of the task-associated dip (20 +/- 1% below baseline) in hippocampal extracellular fluid (ECF) glucose seen in control animals. RH rats also had a larger rise in hippocampal ECF glucose, after intraperitoneal glucose injection, than did controls. However, RH animals tested at acute hypoglycemia ( approximately 2.8 mmol/l) performed significantly worse than control animals. Results were similar in diabetic and nondiabetic rats. Our data suggest that RH causes improvement in subsequent cognitive performance at euglycemia, accompanied by alterations in cognitive metabolism. When glucose availability is limited, complex cognitive functioning seems to be adversely effected in RH animals, perhaps to better maintain and preserve basic brain functions.
反复低血糖（RH）对人类认知的影响仍存在争议，部分原因可能是难以完全控制既往低血糖病史。我们使用非糖尿病和糖尿病大鼠的RH模型，研究短期（每天3小时，共3天）RH对随后海马依赖性空间记忆的影响，分别在血糖正常或急性低血糖状态下进行测试。同时使用微透析测量海马代谢。既往RH改善了血糖正常时的任务表现（非糖尿病RH动物的交替率为79±2%，而对照组为63±3%；P<0.001），同时逆转了对照组动物海马细胞外液（ECF）葡萄糖中与任务相关的下降（比基线低20±1%）。RH大鼠在腹腔注射葡萄糖后，海马ECF葡萄糖的升高也比对照组更大。然而，在急性低血糖（约2.8 mmol/L）状态下测试的RH动物表现明显比对照动物差。糖尿病和非糖尿病大鼠的结果相似。我们的数据表明，RH导致血糖正常时随后的认知表现改善，同时伴有认知代谢的改变。当葡萄糖可利用性有限时，RH动物的复杂认知功能似乎受到不利影响，这可能是为了更好地维持和保留基本脑功能。
