Rossetti L, Hu M
Division of Endocrinology and Diabetes Research and Training Center, Albert Einstein College of Medicine, Bronx, New York 10461.
J Clin Invest. 1993 Dec;92(6):2963-74. doi: 10.1172/JCI116919.
The effects of minimal increments in plasma insulin concentrations on hepatic glucose production and glucose uptake, skeletal muscle net glycogen synthesis and glycogenolysis, glycogen synthase and phosphorylase activity, glucose-6-phosphate and uridinediphosphoglucose (UDPG) concentrations were examined in 24-h and in 6-h fasted conscious rats. Insulin was infused for 120 min at rates of 1.5, 3, 6, 12, 24, and 108 pmol/kg per min in 24-h fasted rats and at rates of 3, 6, 9, 12, 36, and 108 pmol/kg per min in 6-h fasted rats while endogenous insulin release was inhibited by SRIF infusion and plasma glucose was maintained at the basal level. All rats received an infusion of [3-3H]glucose. The portion of the muscle glucose-6-phosphate (G6P) pool derived from net glycogenolysis was estimated from the ratio of specific activities of muscle UDPG and plasma glucose. Minimal increments in the circulating insulin levels, which did not stimulate glucose uptake, caused: (a) the increase in skeletal muscle glycogen synthase activity and the decrease in the rate of muscle glycogenolysis and in the G6P concentration; (b) the inhibition of hepatic glucose production. Net muscle glycogen synthesis was not stimulated despite submaximal activation of glycogen synthase, and its onset correlated with the rise in muscle G6P levels. Thus, insulin's inhibition of muscle glycogenolysis is the most sensitive insulin action on skeletal muscle and its dose-response characteristics resemble those for the inhibition of hepatic glucose production. These findings indicate that skeletal muscle glycogen synthase may play a major role in carbohydrate homeostasis even under postabsorptive (basal insulin) conditions and support the notion that insulin may exert some of its effects on the liver through an indirect or peripheral mechanism.
在禁食24小时和6小时的清醒大鼠中，研究了血浆胰岛素浓度的微小增量对肝脏葡萄糖生成和葡萄糖摄取、骨骼肌净糖原合成与糖原分解、糖原合酶和磷酸化酶活性、葡萄糖-6-磷酸和尿苷二磷酸葡萄糖（UDPG）浓度的影响。在禁食24小时的大鼠中，以1.5、3、6、12、24和108 pmol/kg每分钟的速率输注胰岛素120分钟；在禁食6小时的大鼠中，以3、6、9、12、36和108 pmol/kg每分钟的速率输注胰岛素120分钟，同时通过输注生长抑素抑制内源性胰岛素释放，并将血浆葡萄糖维持在基础水平。所有大鼠均输注[3-3H]葡萄糖。根据肌肉UDPG和血浆葡萄糖的比活性比值估算出由净糖原分解产生的肌肉葡萄糖-6-磷酸（G6P）池的比例。循环胰岛素水平的微小增量并未刺激葡萄糖摄取，但却导致：（a）骨骼肌糖原合酶活性增加，肌肉糖原分解速率和G6P浓度降低；（b）肝脏葡萄糖生成受到抑制。尽管糖原合酶未达到最大激活，但净肌肉糖原合成并未受到刺激，其开始与肌肉G6P水平的升高相关。因此，胰岛素对肌肉糖原分解的抑制是胰岛素对骨骼肌最敏感的作用，其剂量反应特征类似于对肝脏葡萄糖生成的抑制。这些发现表明，即使在吸收后（基础胰岛素）条件下，骨骼肌糖原合酶可能在碳水化合物稳态中发挥主要作用，并支持胰岛素可能通过间接或外周机制对肝脏发挥某些作用的观点。
