INSULIN-DEPRIVED DIABETIC PANCREATIC VENOUS DIVERSION

胰岛素剥夺型糖尿病胰腺静脉分流术

• 批准号: 2291904
• 负责人: RICHARD Nathan BERGMAN
• 金额: $ 2.36万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-09-30 至 1996-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2291904
• 关键词: arginine; arteriovenous shunt surgery; blood glucose; fasting; free fatty acids; glucagon; gluconeogenesis; glycogenolysis; human subject; hyperglucagonemia; hyperglycemia; insulin; insulin dependent diabetes mellitus; liver metabolism; pancreas disorder; pathologic process; physiologic anastomosis

The proposal is for a collaborative research project between the University of Southern California (USC) and the Department of Liver and Metabolic Surgery (DLMS), at the Moscow Sechenov Medical Academy in Russia. R. N. Bergman and T. Buchanan in Los Angeles has long been interested in the pathogenesis and etiology of diabetes mellitus. In particular, he is funded by the NIH (DK29867 -"parent grant") to study the factors which control glucose output by liver. It is clear that the hyperglycemia which characterizes diabetes results from an elevated rate of hepatic glucose output (HGO) in the fasting state, and a reduced ability of insulin to suppress HGO after carbohydrate ingestion. Clearly lack of insulin is an important factor in the overproduction of glucose in the Type 1 ("juvenile-onset") diabetic. Less clear is the possible importance of elevated portal levels of the glycogenolytic, gluconeogenic hormone glucagon. The role of glucagon in hyperglycemia of diabetes, as well as in stress and exercise conditions has been controversial for many years. Confusion has resulted from the inability to specifically suppress glucagon secretion in Type 1 patients. However, a surgical operation pioneered in Moscow by Dr. Galperin should allow us to examine the significance of hyperglucagonemia in the etiology of diabetes. He has performed the spleno-renal venous anastomoses in over 400 diabetic patients in the former Soviet Union (most in Russia). Thus, because the pancreatic venous outflow enters the systemic rather than the portal circulation, it is to be expected that the levels of glucagon entering the liver in the operated patients should be considerably lower than in non- operated diabetic patients. We propose to take advantage of the availability of this large population of operated diabetic patients to evaluate the importance of hyperglucagonemia in the etiology of Type 1 diabetics. Dr. Galperin and his colleagues will perform clinical. protocols in Moscow on 2 groups of diabetic patients: those who have had, and those who have not had the spleno-renal shunt procedure. We will test the hypotheses that I) glucagon levels entering the liver are lower in operated subjects; 2) fasting glucose production rates are lower in operated patients and this is related to the relative hypoglucagonemia; 3) due to lower glucagon, livers of operated patients are more sensitive to insulin due to lower glucagon. Protocols will be performed in Moscow, and plasma samples will be shipped to Los Angeles for chemical and statistical analysis.

该建议是一个合作研究项目之间的 南加州大学（USC）和肝脏和 代谢外科（DLMS），在莫斯科谢切诺夫医学院， 俄罗斯 R. n. Bergman和T.洛杉矶的布坎南长期以来 对糖尿病的发病机理和病因感兴趣。在 特别是，他是由美国国立卫生研究院资助（DK29867-"家长补助金"），研究 控制肝脏葡萄糖输出的因素。很明显 以糖尿病为特征的高血糖症是由于 空腹状态下的肝葡萄糖输出量（HGO）， 胰岛素抑制碳水化合物摄入后HGO的能力。明确 缺乏胰岛素是糖尿病患者体内葡萄糖过度产生的重要因素。 1型（"青少年发病"）糖尿病。不太清楚的是， 门脉糖原分解、糖原合成和糖原合成水平升高的重要性 激素胰高血糖素。胰高血糖素在糖尿病高血糖中的作用， 以及在压力和运动条件下的作用一直是有争议的 年混乱是由于无法具体抑制 1型糖尿病患者的胰高血糖素分泌然而，一个外科手术 由加尔佩林博士在莫斯科开创的，应该让我们检查 高胰高血糖素血症在糖尿病病因中的意义他 对400余例糖尿病患者行脾肾静脉吻合术 前苏联的患者（大部分在俄罗斯）。因此，由于 胰静脉流出物进入全身而不是门静脉 循环中，预期进入血液循环的胰高血糖素水平 手术患者的肝脏应大大低于非手术患者， 糖尿病患者手术。我们建议利用 这一庞大的糖尿病患者手术人群的可用性， 评估高胰高血糖素血症在1型糖尿病病因中的重要性 糖尿病人Galperin博士和他的同事将进行临床。 在莫斯科对2组糖尿病患者的治疗方案： 和那些没有做过脾肾分流术的人。我们将测试 假设I）进入肝脏的胰高血糖素水平较低， 2）空腹血糖生成率较低， 手术患者，这与相对低胰高血糖素血症有关; 3） 由于胰高血糖素较低，手术患者的肝脏对 胰岛素由于低胰高血糖素。方案将在莫斯科执行， 血浆样本将被运送到洛杉矶进行化学和统计分析。 分析.