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.

该提案是关于以下机构之间的合作研究项目： 南加州大学 (USC) 和肝病系 代谢外科 (DLMS)，位于莫斯科谢切诺夫医学院 俄罗斯。 洛杉矶的 R. N. Bergman 和 T. Buchanan 长期以来 对糖尿病的发病机制和病因学感兴趣。在 特别是，他由 NIH（DK29867 -“家长补助金”）资助来研究 控制肝脏葡萄糖输出的因素。很明显， 高血糖是糖尿病的特征，是由血糖升高引起的 空腹状态下肝葡萄糖输出（HGO）的减少 碳水化合物摄入后胰岛素抑制 HGO 的能力。清楚地 胰岛素缺乏是导致葡萄糖生成过多的一个重要因素 1 型（“青少年发病”）糖尿病。不太清楚的是可能的 糖原分解、糖异生的门静脉水平升高的重要性 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情况对于许多人来说一直是有争议的 年。混乱是由于无法专门抑制 1 型患者的胰高血糖素分泌。然而，外科手术 加尔佩林博士在莫斯科开创的应该让我们能够检查 高胰高血糖素血症在糖尿病病因学中的意义。他有 为400多名糖尿病患者进行了脾肾静脉吻合术 前苏联患者（大部分在俄罗斯）。因此，由于 胰静脉流出进入全身系统而不是门静脉 循环中，预计进入循环系统的胰高血糖素水平 接受手术的患者的肝脏水平应显着低于未接受手术的患者 做过手术的糖尿病患者。我们建议利用 大量接受手术的糖尿病患者的可用性 评估高胰高血糖素血症在 1 型病因学中的重要性 糖尿病患者。加尔佩林博士和他的同事将进行临床工作。 在莫斯科对两组糖尿病患者进行的治疗方案：患有、 以及那些没有进行过脾肾分流手术的人。我们将测试 假设 I) 进入肝脏的胰高血糖素水平较低 操作对象； 2) 空腹血糖生成率较低 手术患者，这与相对低血糖有关； 3） 由于胰高血糖素较低，手术患者的肝脏对 由于胰高血糖素较低而需要胰岛素。协议将在莫斯科执行，并且 血浆样本将被运往洛杉矶进行化学和统计 分析。