Wahren John, Ekberg Karin
Department of Molecular Medicine and Surgery, Karolinska Institute, SE-171 77 Stockholm, Sweden.
Annu Rev Nutr. 2007;27:329-45. doi: 10.1146/annurev.nutr.27.061406.093806.
The liver plays a key role for the maintenance of blood glucose homeostasis under widely changing physiological conditions. In the overnight fasted state, breakdown of hepatic glycogen and synthesis of glucose from lactate, amino acids, glycerol, and pyruvate contribute about equally to hepatic glucose production. Postprandial glucose uptake by the liver is determined by the size of the glucose load reaching the liver, the rise in insulin concentration, and the route of glucose delivery. Hepatic glycogen stores are depleted within 36 to 48 hours of fasting, but gluconeogenesis continues to provide glucose for tissues with an obligatory glucose requirement. Glucose output from the liver increases during exercise; during short-term intensive exertion, hepatic glycogenolysis is the primary source of extra glucose for skeletal muscle, and during prolonged exercise, hepatic gluconeogenesis becomes gradually more important in keeping with falling insulin and rising glucagon levels. Type 1 diabetes is accompanied by diminished hepatic glycogen stores, augmented gluconeogenesis, and increased basal hepatic glucose production in proportion to the severity of the diabetic state. The hyperglycemia of type 2 diabetes is in part caused by an overproduction of glucose from the liver that is secondary to accelerated gluconeogenesis.
在广泛变化的生理条件下，肝脏对维持血糖稳态起着关键作用。在空腹过夜状态下，肝糖原分解以及由乳酸、氨基酸、甘油和丙酮酸合成葡萄糖，对肝脏葡萄糖生成的贡献大致相同。餐后肝脏对葡萄糖的摄取取决于到达肝脏的葡萄糖负荷量、胰岛素浓度的升高以及葡萄糖的输送途径。禁食36至48小时内，肝糖原储备耗尽，但糖异生继续为有强制性葡萄糖需求的组织提供葡萄糖。运动期间肝脏的葡萄糖输出增加；在短期高强度运动中，肝糖原分解是骨骼肌额外葡萄糖的主要来源，而在长时间运动中，随着胰岛素水平下降和胰高血糖素水平上升，肝糖异生逐渐变得更加重要。1型糖尿病伴有肝糖原储备减少、糖异生增加，且基础肝脏葡萄糖生成与糖尿病状态的严重程度成比例增加。2型糖尿病的高血糖部分是由肝脏葡萄糖过度生成所致，这继发于糖异生加速。
