Kraft Guillaume, Coate Katie C, Winnick Jason J, Dardevet Dominique, Donahue E Patrick, Cherrington Alan D, Williams Phillip E, Moore Mary Courtney
Department of Molecular Physiology and Biophysics,Vanderbilt University School of Medicine, Nashville, Tennessee; and
Department of Molecular Physiology and Biophysics,Vanderbilt University School of Medicine, Nashville, Tennessee; and.
Am J Physiol Endocrinol Metab. 2017 Sep 1;313(3):E263-E272. doi: 10.1152/ajpendo.00045.2017. Epub 2017 May 23.
The postprandial state is characterized by a storage of nutrients in the liver, muscle, and adipose tissue for later utilization. In the case of a protein-rich meal, amino acids (AA) stimulate glucagon secretion by the α-cell. The aim of the present study was to determine the impact of the rise in glucagon on AA metabolism, particularly in the liver. We used a conscious catheterized dog model to recreate a postprandial condition using a pancreatic clamp. Portal infusions of glucose, AA, and insulin were used to achieve postprandial levels, while portal glucagon infusion was either maintained at the basal level or increased by three-fold. The high glucagon infusion reduced the increase in arterial AA concentrations compared with the basal glucagon level (-23%, < 0.05). In the presence of high glucagon, liver AA metabolism shifted toward a more catabolic state with less protein synthesis (-36%) and increased urea production (+52%). Net hepatic glucose uptake was reduced modestly (-35%), and AA were preferentially used in gluconeogenesis, leading to lower glycogen synthesis (-54%). The phosphorylation of AMPK was increased by the high glucagon infusion (+40%), and this could be responsible for increasing the expression of genes related to pathways producing energy and lowering those involved in energy consumption. In conclusion, the rise in glucagon associated with a protein-rich meal promotes a catabolic utilization of AA in the liver, thereby, opposing the storage of AA in proteins.
餐后状态的特征是营养物质在肝脏、肌肉和脂肪组织中储存以供后续利用。在摄入富含蛋白质的膳食时，氨基酸（AA）会刺激α细胞分泌胰高血糖素。本研究的目的是确定胰高血糖素升高对AA代谢的影响，特别是在肝脏中的影响。我们使用清醒插管犬模型，通过胰腺钳夹来重现餐后状态。通过门静脉输注葡萄糖、AA和胰岛素来达到餐后水平，而门静脉胰高血糖素输注要么维持在基础水平，要么增加三倍。与基础胰高血糖素水平相比，高剂量胰高血糖素输注降低了动脉血AA浓度的升高（-23%，P<0.05）。在高胰高血糖素存在的情况下，肝脏AA代谢转向更具分解代谢的状态，蛋白质合成减少（-36%），尿素生成增加（+52%）。肝脏净葡萄糖摄取适度减少（-35%），AA优先用于糖异生，导致糖原合成降低（-54%）。高剂量胰高血糖素输注使AMPK的磷酸化增加（+40%），这可能是导致与能量产生途径相关的基因表达增加以及与能量消耗相关的基因表达降低的原因。总之，与富含蛋白质的膳食相关的胰高血糖素升高促进了肝脏中AA的分解代谢利用，从而对抗了AA在蛋白质中的储存。
