GLUCOSE HOMEOSTASIS AND THE SURGICALLY ALTERED PANCREAS

胰岛素分泌的调节和由此产生的糖调节过程 还没有完全被理解。在这方面已经做了大量的研究 完整的生物体和模拟病理状态的模型，如 糖尿病。有关这一影响的研究较少。 手术干预可能会对血糖稳态产生影响。这类研究 不仅在预测由于以下原因可能发生的更改方面有价值 手术本身，也在澄清这些过程中的完好无损 有机体。胰腺的外科改变与临床相关性 包括切除、全身引流和自体移植。我们最初的 犬80%胰腺切除(门静脉完整引流)的实验研究 表现为外周低胰岛素血症和改变的葡萄糖处置。 相同胰腺切除但静脉全身分流的动物 流出物使胰岛素水平和葡萄糖处理“正常化”。因此 门静脉的“去胰岛素”似乎会导致纠正 门静脉引流的动物表现为血糖稳态的改变。 全胰腺切除动物及其自体移植 减少的β细胞质量(PAT)同样具有“归一化”值。进一步 对帕特动物的研究表明，它们以一种方式处理葡萄糖 与正常动物一样，其胰岛素分泌已经 被抑制肽，生长抑素所消除。此外，还研究了 自体移植的动物表现出严重的GIP和胰腺缺陷。 多肽(PP)。我们建议检验四个不同的假设 手术改变的正常和非手术状态下的葡萄糖稳态模型 术后动物。首先，在胰腺切除动物中，肝脏 提取强制剂量的胰岛素，该剂量高于所有其他 糖调节过程和结果改变的葡萄糖处置。第二, 肝脏葡萄糖输出量在葡萄糖“正常化”中起着关键作用 门静脉“去胰岛素”时的动态平衡。第三, 不依赖于胰岛素的葡萄糖处理在 当胰岛素被全身排出时，“标准化”的葡萄糖处理。 第四，多肽缺乏状态同样有助于改变 胰腺切除后的糖调节过程，这些过程可以 通过补充这些多肽来纠正。我们相信，通过使用 我们已经建立的动物模型和挑衅性的测试 方法学，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.