Burgos-Ramos Emma, Canelles Sandra, Frago Laura M, Chowen Julie A, Arilla-Ferreiro Eduardo, Argente Jesús, Barrios Vicente
Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Instituto de Investigación La Princesa, Avda. Menéndez Pelayo, 65, E-28009 Madrid, Spain ; Present address : IMDEA Food, CEI UAM + CSIC, Carretera de Cantoblanco 8, Madrid, E-28049 Spain.
Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Instituto de Investigación La Princesa, Avda. Menéndez Pelayo, 65, E-28009 Madrid, Spain ; Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, E-28009 Spain.
Nutr Metab (Lond). 2016 Mar 1;13:19. doi: 10.1186/s12986-016-0079-9. eCollection 2016.
Insulin regulates glucose homeostasis through direct effects on the liver, among other organs, with leptin modulating insulin's hepatic actions. Since central leptin may modify insulin signaling in the liver, we hypothesized that leptin infusion activates hepatic glycogen synthesis following peripheral administration of a bolus of glucose or insulin, thus regulating glycemia.
Oral glucose and intraperitoneal insulin tolerance tests were performed in control, intracerebroventricular leptin-treated and pair-fed rats during 14 days. An improvement in glycemia and an increase in hepatic free glucose and glycogen concentrations after glucose or insulin overload were observed in leptin-treated rats. In order to analyze whether the liver was involved in these changes, we studied activation of insulin signaling by Western blotting and multiplex bead immunoassay after leptin infusion. Our studies revealed an increase in phosphorylation of insulin receptor substrate-1 and Akt in leptin-treated rats. Examination of parameters related to glucose uptake and metabolism in the liver revealed an augment in glucose transporter 2 and a decrease in phosphoenolpyruvate carboxylase protein levels in this group.
These results indicate that central leptin increases hepatic insulin signaling, associated with increased glycogen concentrations after glucose or insulin overload, leading to an improvement in glycemia.
胰岛素通过对肝脏及其他器官的直接作用来调节葡萄糖稳态，瘦素则调节胰岛素的肝脏作用。由于中枢性瘦素可能会改变肝脏中的胰岛素信号，我们推测在外周注射葡萄糖或胰岛素后，输注瘦素会激活肝脏糖原合成，从而调节血糖。
在14天内，对对照组、经脑室注射瘦素处理的大鼠以及配对喂养的大鼠进行了口服葡萄糖耐量试验和腹腔注射胰岛素耐量试验。在经瘦素处理的大鼠中，观察到葡萄糖或胰岛素负荷后血糖改善以及肝脏游离葡萄糖和糖原浓度增加。为了分析肝脏是否参与了这些变化，我们在输注瘦素后通过蛋白质印迹法和多重微珠免疫测定法研究了胰岛素信号的激活情况。我们的研究显示，经瘦素处理的大鼠中胰岛素受体底物-1和Akt的磷酸化增加。对与肝脏葡萄糖摄取和代谢相关参数的检查显示，该组中葡萄糖转运蛋白2增加，磷酸烯醇式丙酮酸羧化酶蛋白水平降低。
这些结果表明，中枢性瘦素增加肝脏胰岛素信号，与葡萄糖或胰岛素负荷后糖原浓度增加相关，从而导致血糖改善。
