NMR STUDIES:HEPATIC GLUCOSE METABOL IN HUMANS EXERCISING

描述(改编自应用程序)运动过程中的血糖 尽管肌肉血糖升高，但浓度保持相对恒定 领悟。这是因为内源性葡萄糖产生(EGP)增加到 与增加的要求相匹配。尽管许多研究已经检验了 激素/神经元对肝脏葡萄糖产生的调节，目前知之甚少 关于发生这种情况的机制(即，糖原分解和/或 糖异生增加)。此外，人们对此知之甚少。 大鼠安静和运动时肝糖原代谢的调节 1型糖尿病患者。最近的研究表明， 受控1型糖尿病受试者的肝糖原储备是 大约三分之一的健康对照组受试者。鉴于……的重要性 肝糖原分解在维持EGP的空腹状态和 可以预见，这一进程在这两个方面都是不足的 这些州中。此应用程序的总体目标是解决这些问题 使用~(13)C核磁共振波谱技术的问题 气相色谱-质谱仪(GC-MS)与磁感应联用 磁共振成像(MRI)无创性检测Net的贡献 安静和运动时肝脏对EGP的糖原分解和糖异生作用 健康和1型糖尿病(控制良好和控制较差)受试者。 这些研究的具体目的是：1)考察肝脏的调节 健康人安静和运动时糖原分解和糖异生 受试者和1型糖尿病患者以及2)确定 肾上腺素和胰高血糖素对肝脏的相对贡献 健康受试者和1型糖尿病受试者的糖原分解和糖异生。这个 将被检验的假设是：1)在健康受试者中， 肝糖原净分解对EGP的贡献将按比例增加 与运动的强度有关。二)相反，控制不良的受试者 1型糖尿病患者肝糖原储备量低，糖异生 是在休息和运动中维持EGP的主要因素， (3)肾上腺素和胰高血糖素主要刺激健康人的EGP 通过增加肝脏净糖原分解，而在患者中 这些激素刺激EGP主要是通过增加 糖异生作用。这些研究的结果应该提供重要的新的 健康人群和1型糖尿病患者肝脏糖代谢调节的研究 糖尿病受试者。

DESCRIPTION (adapted from the application) During exercise plasma glucose concentrations remain relatively constant despite increased muscle glucose uptake. This occurs because endogenous glucose production (EGP) increases to match the increased requirements. Despite many studies that have examined the hormonal/neuronal regulation of hepatic glucose production, little is known about the mechanism by which this occurs (i.e., whether glycogenolysis and/or gluconeogenesis increases). Furthermore, very little is known about the regulation of hepatic glycogen metabolism at rest or during exercise in patients with type 1 diabetes. Recent studies have demonstrated that poorly controlled type 1 diabetic subjects have hepatic glycogen stores that are approximately one-third of healthy control subjects. Given the importance of hepatic glycogenolysis in maintaining EGP in the fasting state and during exercise, it might be anticipated that this process would be deficient in both of these states. The overall goal of this application is to address these questions using 13C nuclear magnetic resonance (NMR) spectroscopy techniques in conjunction with Gas Chromatography Mass Spectroscopy (GC-MS) and magnetic resonance imaging (MRI) to non invasively examine the contributions of net hepatic glycogenolysis and gluconeogenesis to EGP during rest and exercise in healthy and type 1 diabetic (well controlled and poorly controlled) subjects. The specific aims of these studies are: 1) To examine the regulation of hepatic glycogenolysis and gluconeogenesis at rest and during exercise in healthy subjects and in patients with type 1 diabetes and 2) To determine the roles of epinephrine and glucagon on the relative contributions of hepatic glycogenolysis and gluconeogenesis in healthy and type 1 diabetic subjects. The hypotheses that will be tested are i) That in healthy subjects the relative contribution of net hepatic glycogenolysis to EGP will increase in proportion to the intensity of exercise. ii) In contrast, subjects with poorly controlled type 1 diabetes will have low hepatic glycogen stores and gluconeogenesis will be the main factor responsible for sustaining EGP at rest and during exercise, (iii) Epinephrine and glucagon will stimulate EGP in healthy subjects primarily by increasing net hepatic glycogenolysis, whereas in the patients with poorly controlled diabetes these hormones will stimulate EGP mostly by increasing gluconeogenesis. The results of these studies should provide important new insight into the regulation of hepatic glucose metabolism in healthy and type 1 diabetic subjects.