High altitude may alter oxygen availability and renal metabolism in diabetics as measured by hyperpolarized [1-13C]pyruvate magnetic resonance imaging
High altitude may alter oxygen availability and renal metabolism in diabetics as measured by hyperpolarized [1-13C]pyruvate magnetic resonance imaging
复制标题
DOI：
10.1038/ki.2013.504
复制
发表时间：
2014-07-01
影响因子：
19.6
通讯作者：
Ardenkjaer-Larsen, Jan H.
中科院分区：
文献类型：
--
作者：
Laustsen, Christoffer;Lycke, Sara;Ardenkjaer-Larsen, Jan H.
肾脏约占全身耗氧量的10%，而仅占总体重的0.5%。众所周知，肾内缺氧存在于与肾脏疾病发展相关的几种疾病中，包括糖尿病，并且当肾血流不受影响时。生活在高海拔地区的糖尿病患者肾功能的恶化进一步支持了氧代谢紊乱的重要性。因此，我们认为，减少氧气的可用性改变肾脏能量代谢。在这里，我们介绍了一种新的磁共振成像（MRI）方法来监测与糖尿病和氧气供应相关的代谢变化。链脲佐菌素糖尿病大鼠和对照组大鼠给予减少，正常或增加的吸入氧气，以改变组织氧合。使用超极化[1-C-13]丙酮酸盐MRI研究对肾脏氧代谢的影响。减少吸入氧气并没有改变对照组的肾代谢。糖尿病患者肾脏中氧利用率的降低改变了能量代谢，乳酸和丙氨酸的形成分别增加了23%和34%，而碳酸氢盐通量没有变化。因此，高海拔地区糖尿病患者肾病患病率和严重程度的增加可能源于对吸入氧气的敏感性增加。这种增加的乳酸产生将代谢途径转向低氧途径。
The kidneys account for about 10% of the whole body oxygen consumption, whereas only 0.5% of the total body mass. It is known that intrarenal hypoxia is present in several diseases associated with development of kidney disease, including diabetes, and when renal blood flow is unaffected. The importance of deranged oxygen metabolism is further supported by deterioration of kidney function in patients with diabetes living at high altitude. Thus, we argue that reduced oxygen availability alters renal energy metabolism. Here, we introduce a novel magnetic resonance imaging (MRI) approach to monitor metabolic changes associated with diabetes and oxygen availability. Streptozotocin diabetic and control rats were given reduced, normal, or increased inspired oxygen in order to alter tissue oxygenation. The effects on kidney oxygen metabolism were studied using hyperpolarized [1-C-13]pyruvate MRI. Reduced inspired oxygen did not alter renal metabolism in the control group. Reduced oxygen availability in the diabetic kidney altered energy metabolism by increasing lactate and alanine formation by 23% and 34%, respectively, whereas the bicarbonate flux was unchanged. Thus, the increased prevalence and severity of nephropathy in patients with diabetes at high altitudes may originate from the increased sensitivity toward inspired oxygen. This increased lactate production shifts the metabolic routs toward hypoxic pathways.