THE PANCREATIC POLYPEPTIDE FAMILY IN OBESITY

胰多肽、神经肽Y和肽YY是第三家族 从脑肠轴中提取结构相关的肽。 本提案的目的是通过以下方式澄清这些机制： 这些肽控制营养摄入和利用， 确定它们在肥胖症发病机制中的作用。 我们会研究 胰岛多肽对葡萄糖代谢的影响 葡萄糖钳夹技术和离体大鼠脂肪分解 脂肪细胞 其他研究将确定脑池内注射的影响。 注射神经肽Y对食物摄入，胃排空， 体温调节、胰岛素分泌和内脏血流量 标记微球技术。 我们还将确定肽YY 通过脂肪浴释放的回肠粘膜接合回肠制动器， 通过减缓肠道运输增加营养吸收。 在这些 我们将研究肽YY对胃排空的影响， 肠运输和空肠流量的水，电解质和 营养素 初步研究表明，胰淀粉酶和DNA 用肽YY长期治疗可降低含量。 充分 将进行剂量-反应研究，并且该肽对 肠生长测定。 在这些大鼠实验之后，我们将 探讨胰腺缺损的原因及意义 多肽释放最近在先天性肥胖小鼠中被描述。 我们将 研究泛生体之间的超微结构关系， 多肽细胞和其他内分泌细胞在肥大的胰岛内， 肥胖小鼠，并确定胰岛素低血糖的影响， 肾上腺切除术对该动物模型中泛产生的多肽释放的影响。 其他研究将确定胰多肽是否逆转 先天性肥胖症，通过抑制胆汁而诱导吸收不良， 胰腺血流 最后，我们将扩大对异常的调查， 在肥胖小鼠中观察到的神经肽的脑含量。 我们尤其 将比较神经肽Y在肥胖小鼠和瘦小鼠中的分布 强调神经肽Y在脑内的区域分布。 这些 研究将确定该家族控制 为营养素的摄入和利用提供实验依据 为将来胰多肽在治疗肥胖症中的应用提供了参考。

Pancreatic Polypeptide, Neuropeptide Y and Peptide YY are the third family of structurally related peptides to be extracted from the brain-gut axis. The objectives of the present proposal are to clarify the mechanisms by which these peptides control nutrient intake and utilization and to determine their role in the pathogenesis of obesity. We will examine the effects of isologous pancreatic polypeptide upon glucose metabolism using the glucose clamp technique and upon lipolysis using isolated rat adipocytes. Other studies will determine the effects of intracisternal injections of Neuropeptide Y on food intake, gastric emptying, thermoregulation, insulin secretion and splanchnic blood flow using the labelled microsphere technique. We will also determine if Peptide YY released by fat bathing the ileal mucosa engages the ileal-brake which increases absorption of nutrients by slowing intestinal transit. In these studies we will examine the effects of Peptide YY on gastric emptying, intestinal transit and jejunal fluxes of water, electrolytes and nutrients. Preliminary studies demonstrate that pancreatic amylase and DNA contents are reduced by chronic treatment with peptide YY. Full dose-response studies will be performed and the effects of this peptide on intestinal growth determined. Following these experiments in rat, we will investigate the cause and significance of the defect in pancreatic polypeptide release recently decribed in congenitally obese mice. We will examine the ultrastructural relationships between the pancreated polypeptide cell and other endocrine cells within the hypertrophic islet of the obese mouse and determine the effects of insulin hypoglycemia and adrenalectomy on pancreated polypeptide release in this animal model. Other studies will determine whether pancreatic polypeptide reverses congenital obesity by inducing malabsorption through inhibition of bile and pancreatic flow. Finally we will expand our investigations on the abnormal brain content of the neuropeptide observed in obese mice. In particular we will compare the distribution of neuropeptide Y in obese and lean mice emphasizing the regional distribution of neuropeptide Y in brain. These studies will determine the mechanisms by which this family controls nutrient intake and utilization and could provide the experimental basis for the future use of pancreatic polypeptide in the treatment of obesity.