Evans M L, Hopkins D, Macdonald I A, Amiel S A
Department of Medicine, University of Cambridge, Box 157 Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, UK.
Diabet Med. 2004 May;21(5):440-6. doi: 10.1111/j.1464-5491.2004.01174.x.
To investigate the potential for the non-glucose metabolic substrate alanine to support brain function during glucose deprivation in man.
Seven healthy men were studied on two occasions using a hyperinsulinaemic glucose clamp to lower arterialized plasma glucose to 2.5 mmol/l, in the presence of either 2 mmol/kg/h alanine infusion or saline, measuring counter-regulatory hormonal responses, symptoms generated and cognitive function with a mini-battery of tests sensitive to hypoglycaemia.
Alanine infusion elevated plasma alanine (peak value 1481 +/- 1260 vs. 138 +/- 32 micro mol/l, P = 0.02 alanine vs. saline) and lactate (peak value 3.09 +/- 0.14 vs. 2.05 +/- 0.12 mmol/l, P = 0.02). Cognitive function assessed by the Stroop word and colour subtests deteriorated less with alanine than saline (P < 0.01 for both). Other cognitive function tests deteriorated equally and counter-regulatory hormones rose equally during hypoglycaemia in both studies (P > 0.34) except for increased glucagon with alanine (peak 260 +/- 53 vs. 91 + 8 ng/l, P = 0.03). There was no significant effect of alanine on either autonomic or neuroglycopenic symptom scores.
Some, but not all, aspects of cognitive performance may be supported by an alanine infusion during hypoglycaemia. It is not clear whether alanine supports brain function directly or via increased availability of lactate. These data contribute to the growing evidence that regional metabolic differences exist in the brain's ability to use non-glucose fuels during hypoglycaemia.
研究在人体葡萄糖缺乏期间，非葡萄糖代谢底物丙氨酸支持脑功能的潜力。
对7名健康男性进行了两次研究，采用高胰岛素-正常血糖钳夹技术将动脉化血浆葡萄糖水平降至2.5 mmol/L，分别给予2 mmol/kg/h丙氨酸输注或生理盐水，测量对抗调节激素反应、产生的症状以及通过一组对低血糖敏感的测试评估认知功能。
丙氨酸输注使血浆丙氨酸升高（峰值为1481±1260 vs. 138±32 μmol/L，丙氨酸组与生理盐水组相比，P = 0.02）以及乳酸升高（峰值为3.09±0.14 vs. 2.05±0.12 mmol/L，P = 0.02）。通过Stroop文字和颜色子测试评估的认知功能，丙氨酸组比生理盐水组恶化程度更小（两者P均<0.01）。在两项研究中，除丙氨酸组胰高血糖素升高（峰值为260±53 vs. 91±8 ng/L，P = 0.03）外，其他认知功能测试在低血糖期间恶化程度相同，对抗调节激素升高程度也相同（P>0.34）。丙氨酸对自主神经或神经低血糖症状评分均无显著影响。
低血糖期间丙氨酸输注可能支持部分而非全部认知表现方面。尚不清楚丙氨酸是直接支持脑功能还是通过增加乳酸可用性来支持。这些数据进一步证明了低血糖期间大脑利用非葡萄糖燃料的能力存在区域代谢差异。
