Tompkins C V, Brandenburg D, Jones R H, Sönksen P H
Diabetologia. 1981 Feb;20(2):94-101. doi: 10.1007/BF00262008.
A [14C]-glucose tracer infusion method was used to compare the effects of insulin infusion on glucose metabolism with the effects of infusion of three semisynthetic modified insulins and of proinsulin. Insulin produced hypoglycaemia in the anaesthetised dog by decreasing hepatic glucose production and increasing peripheral glucose utilisation. Compensatory antihypoglycaemic mechanisms eventually modified these responses. A1, B29-Diacetyl insulin exerted an hypoglycaemic effect entirely by stimulation of peripheral glucose uptake. A1-B29 crosslinked insulins and proinsulin produced hypoglycaemia almost entirely by decreasing hepatic glucose production and had little effect on tissue uptake. These observations suggest that insulin analogues may have actions in vivo that are qualitatively different from those of native insulin and suggest that certain analogues have a predominant action on the liver. This has important therapeutic implications concerning the development of semisynthetic insulins for clinical use.
采用[14C] -葡萄糖示踪剂输注法，比较胰岛素输注对葡萄糖代谢的影响与三种半合成修饰胰岛素及胰岛素原输注的影响。胰岛素通过降低肝脏葡萄糖生成和增加外周葡萄糖利用，使麻醉犬出现低血糖。代偿性抗低血糖机制最终改变了这些反应。A1、B29 -二乙酰胰岛素完全通过刺激外周葡萄糖摄取发挥降糖作用。A1 - B29交联胰岛素和胰岛素原几乎完全通过降低肝脏葡萄糖生成产生低血糖，对组织摄取影响很小。这些观察结果表明，胰岛素类似物在体内的作用可能在性质上与天然胰岛素不同，并且表明某些类似物对肝脏有主要作用。这对于开发用于临床的半合成胰岛素具有重要的治疗意义。
