Transgenic approach for the study of physiological roles of pancreatic polypeptide

研究胰多肽生理作用的转基因方法

• 批准号: 09671057
• 负责人: INUI Akio
• 金额: $ 1.92万
• 依托单位: Kobe University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09671057/
• 关键词: pancreatic polypeptide; knockout mouse; feeding behabior; gastric motility; transgenic mouse; body weight regulatory; Pancreatic polypeptide; ノックアウトマウス; トランスジェニックマウス

Background & Aims : Pancreatic polypeptide (PP)is a 36-amino acid hormone produced by F cells within the pancreatic islets and the exocrine pancreas. The definitive function of PP in mammalian physiology still remains to be determined. This study was designed to examine the effects of chronic overexpression or deletion of PP through the development of PP transgenic mice. Methods : PP transgenic mice were created by using mouse PP cDNA under the control of the cytomegalovirus immediate early enhancer-chicken b-actin hybrid promoter (pCAGGS expression vector). Results : A unique line of transgenic mice were created that overexpress PP in the pancreatic islet with low levels of expression in other tissues including the brain. Plasma PP concentrations were more than 20 times higher than those of control littermates. PP transgenic mice gained less weight with specifically reduced food intake and fat mass compared to controls, results which were more evident in male than in female mice. The transgenic mice exhibited a reduced rate of gastric emptying of a solid meal but had normal oxygen consumption and fasting leptin levels. Immunoneutralization with anti-PP antiserum reversed the phenotypic changes of transgenic animals. Conclusions : These results indicate that PP could be involved in feeding and body weight regulation partly through regulation of gastric emptying.

背景与目的：胰多肽（PP）是由胰岛和胰腺外分泌部的F细胞产生的一种由36个氨基酸组成的激素。PP在哺乳动物生理学中的明确功能仍有待确定。本研究旨在通过PP转基因小鼠的发展来检查PP的慢性过表达或缺失的影响。研究方法：将小鼠PP cDNA置于巨细胞病毒即刻早期增强子-鸡b肌动蛋白杂合启动子（pCAGGS表达载体）的控制下，建立PP转基因小鼠。结果如下：创建了一种独特的转基因小鼠品系，其在胰岛中过表达PP，而在包括脑在内的其他组织中表达水平较低。血浆PP浓度比对照同窝仔高20倍以上。与对照组相比，PP转基因小鼠体重增加较少，食物摄入量和脂肪量特别减少，雄性小鼠的结果比雌性小鼠更明显。转基因小鼠表现出固体食物胃排空率降低，但氧消耗和空腹瘦素水平正常。用抗PP抗血清进行免疫中和可逆转转基因动物的表型改变。结论：PP可能通过调节胃排空而参与摄食和体重调节。

项目成果

A Inui: "Neunpeptide Y feeding receptors:ace multiple subtypes involved?" Treuds Pharmacol. Sci.20. 43-46 (1999)

A Inui：“神经肽 Y 喂养受体：涉及多种亚型？”

M.Okita,A.Inui et al.: "Effects of corticotropin-releasing factor on feeding and pancreatic polypeptide response in the dog." J.Endocrinol. 156. 359-364 (1998)

M.Okita，A.Inui 等人：“促肾上腺皮质激素释放因子对狗进食和胰多肽反应的影响”。

A.Inui: "Neuropeptide Y feeding receptors : are multiple subtypes involved?" Trends Pharmacol.Sci.20. 43-46 (1999)

A.Inui：“神经肽 Y 喂养受体：是否涉及多种亚型？”

M.Okita,A.Inui et al.: "Central cholinergic regulation of pancreatic polypeptide secretion in conscious dogs" J.Enducvinol.154. 311-317 (1997)

M.Okita，A.Inui 等人：“清醒狗胰腺多肽分泌的中枢胆碱能调节”J.Enducvinol.154。

M.Okita, A.Inui et al.: "Effects of corticotoropin-releasing factor on feeding and pancreatic polypeptide response in the dog." J.Endocrinol. 156. 359354 (1998)

M.Okita、A.Inui 等人：“皮质激素释放因子对狗进食和胰多肽反应的影响”。