Glucose intolerance but normal satiety in mice with a null mutation in the glucagon-like peptide 1 receptor gene
Glucose intolerance but normal satiety in mice with a null mutation in the glucagon-like peptide 1 receptor gene
复制标题
DOI：
10.1038/nm1196-1254
复制
发表时间：
1996-11-01
期刊：
影响因子：
82.9
通讯作者：
Drucker, DJ
中科院分区：
文献类型：
--
作者：
Scrocchi, LA;Brown, TJ;Drucker, DJ
胰高血糖素样肽 1 (GLP1) 被认为可以调节血糖和饱腹感，但 GLP1 作为肠降血糖素和神经肽的生物学重要性仍存在争议。营养诱导的胰岛素分泌的调节依赖于肠促胰岛素的分泌，肠促胰岛素是肠道衍生的肽，可增强胰岛的胰岛素分泌。为了确定 GLP1 作为摄食行为和胰岛素分泌调节剂的相对生理重要性，我们培育了靶向破坏 GLP1 受体基因 (GLP1R) 的小鼠。这些 GLP1R(-/-) 小鼠能够存活，发育正常，但表现出循环胰岛素。令人惊讶的是，它们在腹膜内葡萄糖激发后也表现出异常水平的血糖。脑室内注射 GLP1 可抑制野生型小鼠的摄食，但不会抑制 GLP1R(-/-) 小鼠的摄食；然而，在 GLP1R(-/-) 小鼠中没有观察到体重或进食行为异常的证据。这些观察结果表明，GLP1 在血糖调节中发挥着核心作用；然而，中枢神经系统中 GLP1/GLP1R 信号传导的破坏与体内摄食行为或肥胖的扰动无关。
Glucagon-like peptide 1 (GLP1) is postulated to regulate blood glucose and satiety, but the biological importance of GLP1 as an incretin and neuropeptide remains controversial. The regulation of nutrient-induced insulin secretion is dependent on the secretion of incretins, gut-derived peptides that potentiate insulin secretion from the pancreatic islets'. To ascertain the relative physiological importance of GLP1 as a regulator of feeding behavior and insulin secretion, we have generated mice with a targeted disruption of the GLP1 receptor gene (GLP1R). These GLP1R(-/-) mice are viable, develop normally but exhibit circulating insulin. It is surprising that they also exhibit abnormal levels of blood glucose following intraperitoneal glucose challenge. Intracerebroventricular administration of GLP1 inhibited-feeding in wild-type mice but not in GLP1R(-/-) mice; however, no evidence for abnormal body weight or feeding behavior was observed in GLP1R(-/-) mice. These observations demonstrate that GLP1 plays a central role in the regulation of glycemia; however, disruption of GLP1/GLP1R signaling in the central nervous system is not associated with perturbation of feeding behavior or obesity in vivo.