Increased brain monocarboxylic acid transport and utilization in type 1 diabetes
Increased brain monocarboxylic acid transport and utilization in type 1 diabetes
复制标题
DOI：
10.2337/diabetes.55.04.06.db05-1325
复制
发表时间：
2006-04-01
期刊：
影响因子：
7.7
通讯作者：
Shulman, GI
中科院分区：
文献类型：
--
作者：
Mason, GF;Petersen, KF;Shulman, GI
我们假设，大脑对非葡萄糖底物(单羧酸[MCAS])的利用能力通过上调MCA转运蛋白而增加，这可能是低血糖时代谢底物的贡献。为了验证这一假设，我们使用C-13磁共振波谱评估了5名控制良好的1型糖尿病受试者和6名非糖尿病对照组受试者在低血糖期间注射[2-C-13]醋酸酯(类似于55 mg/dl)时的脑醋酸酯代谢。醋酸盐通过MCA转运蛋白进入大脑，MCA转运蛋白也用于乳酸和酮。糖尿病患者的脑醋酸酯浓度是对照组的两倍多(P=0.01)。糖尿病患者的醋酸盐氧化代谢率(P=0.015.0 1)和大脑中动脉转运率(P=0.0 1)也是糖尿病患者的近两倍。我们得出结论，在低血糖期间，控制良好的1型糖尿病患者大脑中MCA的转运几乎增加了两倍，这反映在较高的脑醋酸盐浓度和醋酸盐氧化速率上。在胰岛素诱导的低血糖期间，这种上调可能会使包括乳酸在内的其他JAAs的转运增加类似的两倍。这些数据与MCA转运上调可能有助于在1型糖尿病患者低血糖期间维持脑能量供应的假设是一致的。
We hypothesized that increased capacity for brain utilization of nonglucose substrates (monocarboxylic acids [MCAs]) by upregulation of the MCA transporters may contribute metabolic substrates during hypoglycemia. To test this hypothesis, we assessed brain acetate metabolism in five well-controlled type 1 diabetic subjects and six nondiabetic control subjects using C-13 magnetic resonance spectroscopy during infusions of [2-C-13]acetate during hypoglycemia (similar to 55 mg/dl). Acetate is transported into the brain through MCA transporters that are also used for lactate and ketones. Brain acetate concentrations were over twofold higher in the subjects with diabetes than the control subjects (P = 0.01). The fraction of oxidative metabolism from acetate (P = 0.015) and the rate of MCA transport (P = 0.01) were also approximately twofold higher in the diabetic subjects. We conclude that during hypoglycemia MCA transport in the brain was increased by appoximately twofold in patients with well-controlled type 1 diabetes, as reflected by higher brain acetate concentrations and rates of acetate oxidation. This upregulation would potentially allow a similar twofold increase in the transport of other JACAs, including lactate, during insulin-induced hypoglycemia. These data are consistent with the hypothesis that upregulation of MCA transport may contribute to the maintenance of brain energetics during hypoglycemia in patients with type 1 diabetes.