Glucose tolerance improves significantly upon consuming a second, identical meal later in the day (second meal phenomenon). We previously established that morning hyperinsulinemia primes the liver for increased afternoon hepatic glucose uptake (HGU). Although the route of insulin delivery is an important determinant of the mechanisms by which insulin regulates liver glucose metabolism (direct hepatic vs indirect insulin action), it is not known if insulin’s delivery route affects the second meal response. To determine whether morning peripheral insulin delivery (as occurs clinically, i.e. subcutaneous) can enhance afternoon HGU, conscious dogs were treated in the morning with insulin delivered either via the portal vein or peripherally (leg vein), while glucose was infused to maintain euglycemia. Consequently, arterial insulin levels increased similarly in both groups, but relative hepatic insulin deficiency occurred with peripheral insulin delivery. In the afternoon, all animals were challenged with the same hyperinsulinemichyperglycemic clamp to simulate identical postprandial-like conditions. The substantial enhancement of HGU in the afternoon caused by morning portal vein insulin delivery was lost when insulin was delivered peripherally. This indicates that morning insulin does not cause the second meal phenomenon via its indirect actions on the liver, but rather through direct activation of hepatic insulin signaling.

中文翻译：

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改善下午肝脏葡萄糖的处理和储存需要早上肝脏胰岛素受体的参与


在当天晚些时候吃第二顿相同的饭后，葡萄糖耐量会显着改善（第二餐现象）。我们之前确定，早晨高胰岛素血症使肝脏下午肝脏葡萄糖摄取 （HGU） 增加。尽管胰岛素输送途径是胰岛素调节肝脏葡萄糖代谢机制（肝脏直接作用与间接胰岛素作用）的重要决定因素，但尚不清楚胰岛素的输送途径是否会影响第二餐反应。为了确定早晨外周胰岛素输送（如临床上发生的那样，即皮下注射）是否可以增强下午 HGU，清醒的狗在早上通过门静脉或外周（腿部静脉）输送胰岛素进行治疗，同时注入葡萄糖以维持血糖正常。因此，两组的动脉胰岛素水平升高相似，但相对肝胰岛素缺乏发生在外周胰岛素输送时。下午，所有动物都使用相同的高胰岛素高血糖钳夹激发，以模拟相同的餐后样情况。早晨门静脉胰岛素输送引起的下午 HGU 的显著增强在胰岛素外周输送时丢失。这表明早晨胰岛素不是通过其对肝脏的间接作用而引起的二餐现象，而是通过直接激活肝脏胰岛素信号传导。