Hanks J B, Andersen D K, Wise J E, Putnam W S, Meyers W C, Jones R S
Endocrinology. 1984 Sep;115(3):1011-8. doi: 10.1210/endo-115-3-1011.
The hepatic extractions of gastric inhibitory polypeptide (GIP) and insulin were determined using in vitro and in vivo methods to assess the role of the liver in GIP metabolism and the possible effect of GIP on the hepatic extraction of insulin. During in vitro studies using the isolated perfused rat liver, infusion of GIP (2000 pg/ml) alone and in combination with porcine insulin (200 microU/ml) resulted in negligible hepatic extraction of immunoreactive GIP (IR-GIP) in both fed and fasted animals during either physiologically euglycemic or hyperglycemic perfusions. Hepatic extraction of insulin, however, ranged from 26-36% in fasted animals and from 7-25% in fed animals. Hepatic extraction of insulin and net hepatic glucose appearance were minimally affected by GIP. In vivo studies in awake dogs were then performed, in which simultaneous portal and peripheral venous levels of IR-GIP, immunoreactive insulin (IRI), and glucose were assessed after intraduodenal glucose administration. The portal to peripheral (PORT/PERI) venous ratio of endogenous IRI and IR-GIP reflected the findings of the in vitro studies; the PORT/PERI ratio of IRI levels rose from a basal value of 1.9 +/- 0.3 to a peak of 3.7 +/- 0.9, while the PORT/PERI ratio of IR-GIP levels rose from a basal value of 1.0 +/- 0.1 to a peak of 1.4 +/- 0.2, then rapidly returned to 1.0. The in vivo data are consistent with a continuous hepatic extraction of 40-50% of the insulin entering the liver and a negligible hepatic extraction of IR-GIP. We conclude that hepatic extraction of GIP in vitro or in vivo is minimal. In addition, while the fed state of the animal before infusion can result in changes in the in vitro hepatic extraction of insulin, GIP does not mediate these changes.
采用体外和体内方法测定胃抑制性多肽（GIP）和胰岛素的肝脏摄取，以评估肝脏在GIP代谢中的作用以及GIP对胰岛素肝脏摄取的可能影响。在使用离体灌注大鼠肝脏的体外研究中，单独输注GIP（2000 pg/ml）以及与猪胰岛素（200 μU/ml）联合输注时，无论是在生理血糖正常或高血糖灌注期间，进食和禁食动物的肝脏对免疫反应性GIP（IR-GIP）的摄取均可忽略不计。然而，禁食动物肝脏对胰岛素的摄取范围为26%-36%，进食动物为7%-25%。GIP对胰岛素的肝脏摄取和肝脏葡萄糖净出现量影响极小。随后对清醒犬进行了体内研究，在十二指肠内给予葡萄糖后，评估了IR-GIP、免疫反应性胰岛素（IRI）和葡萄糖的门静脉和外周静脉同时水平。内源性IRI和IR-GIP的门静脉与外周（PORT/PERI）静脉比值反映了体外研究结果；IRI水平的PORT/PERI比值从基础值1.9±0.3升至峰值3.7±0.9，而IR-GIP水平的PORT/PERI比值从基础值1.0±0.1升至峰值1.4±0.2，然后迅速回到1.0。体内数据与进入肝脏的胰岛素有40%-50%被肝脏持续摄取以及肝脏对IR-GIP的摄取可忽略不计一致。我们得出结论，体外或体内肝脏对GIP的摄取极少。此外，虽然输注前动物的进食状态可导致体外肝脏对胰岛素摄取的变化，但GIP并不介导这些变化。
