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GLUCOSE HOMEOSTASIS AND THE SURGICALLY ALTERED PANCREAS

葡萄糖稳态和手术改变的胰腺

基本信息

批准号：
3463239
负责人：
JOHN B HANKS
金额：
$ 9.42万
依托单位：
UNIVERSITY OF VIRGINIA
依托单位国家：
美国
项目类别：
财政年份：
1988
资助国家：
美国
起止时间：
1988-01-01 至 1990-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3463239
关键词：
denervation dogs glucose metabolism glucose tolerance test hormone regulation /control mechanism insulin liver metabolism pancreas pancreas transplantation pancreatectomy somatostatin

项目摘要

Glucoregulation of insulin release is poorly understood both in normal intact organisms as well as those altered by disease processes. Chronic studies of models of the surgically altered pancreas allow understanding of certain disease processes (reduced beta cell mass - diabetes) as well as applicability of surgery in treatment (pancreas transplantation). Our preliminary findings have documented the important consequences of portal to systemic release of insulin as well as "insulin-independent" effects on peripheral glucose disposal. These observations have relevance in evaluating three surgical alterations of the pancreas which have pathophysiologic consequence - reduced beta cell mass (80% pancreatectomy), systemic release of insulin (spleno-caval diversion) and denervation (autotransplantation). This proposal intends to expand our preliminary findings by continued observations of intravenous and oral glucose challenge on chronic models of the surgically altered pancreas. Additionally, we propose further studies that allow more sophisticated analysis of hepatic glucose output after "de-insulination" of the portal vein. The response of decreased beta cell mass to sulfonylurea treatment will be studied. Studies employing "steady state" hyperglycemic glucose infusions will be done to study the modulating effects of peptides which suppress (somatostatin) or stimulate (GIP) insulin secretion. Finally, continued studies on "insulin-independent" glucose disposal will allow further understanding of what appears to be a large fraction of glucose handling in the periphery which occurs in the absence of the hormone. We will determine whether this explains the effects of surgery on already documented changes in glucose disposal post- operatively. This studies will allow basic observations about physiologic glucoregulation of insulin release as well as the consequences of surgical alterations of the pancreas which might be employed for treatment of disease processes.

胰岛素释放的糖调节在两个方面都知之甚少，正常完整的生物体以及那些被疾病改变的生物体流程. 手术改变的模型的慢性研究胰腺可以让我们了解某些疾病的过程（β细胞量减少-糖尿病）以及手术治疗（胰腺移植）。我们的初步调查结果记录了门户网站的重要后果，胰岛素的全身释放以及“胰岛素非依赖性”效应外周葡萄糖的处理这些意见具有相关性在评估胰腺的三个手术改变，具有病理生理后果-β细胞质量减少（80%）胰腺切除术）、胰岛素的全身释放（脾腔静脉转移）和去神经（自体移植）。这项建议打算继续扩大我们的初步调查结果，静脉和口服葡萄糖激发对慢性乙型肝炎的观察手术改变的胰腺模型。另外我们建议进行进一步的研究，以便对门静脉“去胰岛素化”后的肝葡萄糖输出。磺脲类药物对β细胞群减少的影响将进行治疗研究。采用“稳态”的研究将进行高血糖葡萄糖输注，以研究抑制（生长抑素）或刺激胰岛素分泌。最后，继续研究 “胰岛素非依赖性”葡萄糖处置将允许进一步的了解葡萄糖的大部分成分在缺乏的情况下发生的周边处理激素. 我们将确定这是否解释了对已经记录的葡萄糖处置后的变化进行手术有效地这项研究将允许基本的观察，胰岛素释放的生理性葡萄糖调节以及胰腺手术改变的后果，用于治疗疾病过程。