GLUCOSE HOMEOSTASIS AND THE SURGICALLY ALTERED PANCREAS

胰岛素分泌的调节和由此产生的葡萄糖调节过程 还没有完全被理解。 在这方面进行了大量的研究， 完整生物体和模拟病理状态的模型， 糖尿病 较少的研究已经完成，其中涉及的影响， 手术干预对葡萄糖稳态的影响。 此类研究 不仅在预测可能发生的变化方面有价值， 手术本身，而且在阐明这些过程中的完整性， 有机体 具有临床意义的胰腺外科改变 包括切除、全身引流和自体移植。 我们最初 在80%胰腺切除术（和完整门静脉引流）的犬中进行的研究 显示外周低胰岛素血症和改变的葡萄糖处置。 相同胰腺切除术但全身静脉分流的动物 流出物具有“标准化的”胰岛素水平和葡萄糖处置。 因此 门静脉的“去胰岛素化”似乎导致了 门静脉引流的动物显示葡萄糖稳态改变。 全胰腺切除和自体移植的动物 减少的β细胞质量（PAT）同样具有“标准化”值。 进一步 对PAT动物的研究表明， 与正常动物的胰岛素分泌相同， 被抑制肽生长抑素消除 此外，研究 自体移植的动物表现出GIP和胰腺的严重缺陷， 多肽（PP）。 我们建议测试四个独立的假设，从这些 手术改变的模型，涉及正常和 术后动物 首先，在胰腺切除动物中，肝脏 提取强制量的胰岛素， 葡萄糖调节过程并导致改变的葡萄糖处置。 第二、 肝葡萄糖输出在葡萄糖“正常化”中起关键作用 当门静脉“去胰岛素化”时， 第三、 胰岛素非依赖性葡萄糖处理在 当胰岛素被全身性排出时，“正常化”的葡萄糖处置。 第四，肽缺乏状态同样有助于改变 胰腺切除术后的葡萄糖调节过程，这些过程可以是 通过补充这些肽进行校正。 我们认为，通过使用 我们已经建立的动物模型和挑衅性的测试 方法，我们将能够评估手术的效果 以一种独特的方式改变胰腺。

Regulation of insulin secretion and the resultant glucoregulatory processes are not completely understood. Considerable research has been done in the intact organism and in models which mimic pathologic states such as diabetes. Less research has been completed which deals with the effect that surgical intervention might have on glucose homeostasis. Such studies are valuable not only in predicting what alterations might occur because of the surgery itself, but also in clarifying these processes in the intact organism. Surgical alterations of the pancreas with clinical relevance include resection, systemic drainage and autotransplantation. Our initial studies in dogs with 80% pancreatectomy (and intact portal drainage) demonstrate peripheral hypoinsulinemia and altered glucose disposal. Animals with the same pancreatectomy but with systemic diversion of venous effluent have "normalized" insulin levels and glucose disposal. Therefore "de-insulinization" of the portal vein appears to result in a correction of the altered glucose homeostasis shown by the animals with portal drainage. Animals with total pancreatectomy and autotransplantation of this same reduced beta cell mass (PAT) likewise have "normalized" values. Further studies in PAT animals show that they dispose of glucose in a fashion identical to that of a normal animal whose insulin secretion has been abolished by the suppressor peptide, somatostatin. In addition, studies of the autotransplanted animals show severe deficiencies of GIP and pancreatic polypeptide (PP). We propose to test four separate hypotheses from these surgically altered models concerning glucose homeostasis in normal and postoperative animals. First, in the pancreas resection animals, the liver extracts a mandatory amount of insulin which overrides all other glucoregulatory processes and results in altered glucose disposal. Second, hepatic glucose output plays a key role in "normalization" of glucose homeostasis when the portal vein is "de-insulinized". Third, insulin-independent glucose disposal plays an important part in the "normalized" glucose disposal when insulin is drained systemically. Fourth, the peptide deficiency state likewise contributes to the altered glucoregulatory processes after pancreatic resection and these can be corrected by supplementation with these peptides. We believe that by use of our already established animal models and provocative test methodologies, we will be able to evaluate the effect of surgical alteration of the pancreas in a unique fashion.