CIBER de Diabetes y Enfermedades Metabólicas Asociadas, Barcelona, Spain.
Am J Physiol Endocrinol Metab. 2012 May 15;302(9):E1070-7. doi: 10.1152/ajpendo.00495.2011. Epub 2012 Feb 14.
Developing brains are vulnerable to nutritional insults. Early undernutrition alters their structure and neurochemistry, inducing long-term pathological effects whose causal pathways are not well defined. During suckling, the brain uses glucose and ketone bodies as substrates. Milk is a high-fat low-carbohydrate diet, and the liver must maintain high rates of gluconeogenesis and ketogenesis to address the needs of these substrates. Insulin and glucagon play major roles in this adaptation: throughout suckling, their blood concentrations are low and high, respectively, and the liver maintains low insulin sensitivity and increased glucagon responsiveness. We propose that disturbances in the endocrine profile and available plasma substrates along with undernutrition-related changes in brain cortex capacity for ketone utilization may cause further alterations in some brain functions. We explored this hypothesis in 10-day-old suckling rats whose mothers were severely food restricted from the 14th day of gestation. We measured the plasma/serum concentrations of glucose, ketone body, insulin and glucagon, and hepatic insulin and glucagon responses. Undernutrition led to hypoglycemia and hyperketonemia to 84% (P < 0.001) and 144% (P < 0.001) of control values, respectively. Liver responsiveness to insulin and glucagon became increased and reduced, respectively; intraperitoneal glucagon reduced liver glycogen by 90% (P < 0.01) in control and by 35% (P < 0.05) in restricted. Cortical enzymes of ketone utilization remained unchanged, but their carrier proteins were altered: monocarboxylate transporter (MCT) 1 increased: 73 ± 14, controls; 169 ± 20, undernourished (P < 0.01; densitometric units); MCT2 decreased: 103 ± 3, controls; 37 ± 4, undernourished (P < 0.001; densitometric units). All of these changes, coinciding with the brain growth spurt, may cause some harmful effects associated with early undernutrition.
发育中的大脑容易受到营养损伤。早期的营养不良会改变大脑的结构和神经化学，诱导长期的病理性影响，但其因果途径尚不清楚。在哺乳期间，大脑使用葡萄糖和酮体作为底物。牛奶是一种高脂肪、低碳水化合物的饮食，肝脏必须维持高葡萄糖生成率和酮生成率，以满足这些底物的需求。胰岛素和胰高血糖素在这种适应中起着重要作用：在整个哺乳期间，它们的血液浓度分别较低和较高，肝脏维持低胰岛素敏感性和增加胰高血糖素反应性。我们提出，内分泌谱和可用血浆底物的紊乱，以及与营养不良相关的大脑皮层酮利用能力的变化，可能导致某些大脑功能的进一步改变。我们在 10 日龄哺乳大鼠中探索了这一假设，这些大鼠的母亲从妊娠第 14 天起就受到严重的食物限制。我们测量了血浆/血清中的葡萄糖、酮体、胰岛素和胰高血糖素浓度，以及肝脏对胰岛素和胰高血糖素的反应。营养不良导致低血糖和高酮血症，分别为对照组的 84%（P<0.001）和 144%（P<0.001）。肝脏对胰岛素和胰高血糖素的反应性分别增加和减少；腹腔内注射胰高血糖素使对照组肝脏糖原减少 90%（P<0.01），使限制组减少 35%（P<0.05）。酮体利用的皮质酶保持不变，但它们的载体蛋白发生了改变：单羧酸转运蛋白（MCT）1 增加：73±14，对照组；169±20，营养不良组（P<0.01；密度计单位）；MCT2 减少：103±3，对照组；37±4，营养不良组（P<0.001；密度计单位）。所有这些变化都与大脑生长突增同时发生，可能导致与早期营养不良相关的一些有害影响。
