Transient insulin deprivation with concurrent hyperglucagonemia is a catabolic state that can occur in type 1 diabetes. To evaluate glucagon’s catabolic effect in the setting of its glucogenic effect, we measured the regional exchanges of amino-metabolites across muscle and splanchnic beds in 16 healthy humans during either somatostatin followed by glucagon or a saline infusion alone. Despite a ≥2-fold increase in the regional exchange of amino-metabolites by glucagon, whole body kinetics and concentrations of amino acids (AAs) remained stable. Glucagon increased the splanchnic uptake of not only gluconeogenic but also essential amino acids (EAAs) while increasing their release from the muscle bed. Regional tracer-based kinetics and 3-methyl-histidine release indicate that EAA release from muscle is likely caused by reduced protein synthesis rather than increased protein degradation. Furthermore, many metabolites known to affect insulin action and metabolism were altered by hyperglucagonemia including increase in branched amino acids and keto acids of leucine and isoleucine in arterial plasma. Further, an increase in arterial concentrations of α-aminoadipic acid arising from increased conversion from lysine in the splanchnic bed was noted. These results demonstrate that hyperglucagonemia during hypoinsulinemia increases net muscle protein catabolism and substantially increases the exchange of amino metabolites across splanchnic and muscle beds.

中文翻译：

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胰岛素缺乏期间胰高血糖素对蛋白质分解代谢的影响 - 骨骼肌和内脏床的氨基酸交换

暂时性胰岛素剥夺伴并发高胰高血糖素血症是 1 型糖尿病中可能发生的一种分解代谢状态。为了评估胰高血糖素在生糖作用下的分解代谢作用，我们测量了 16 名健康人在服用生长抑素后服用胰高血糖素或单独注射生理盐水期间，肌肉和内脏床中氨基代谢物的区域交换。尽管胰高血糖素引起的氨基代谢物区域交换增加了 2 倍以上，但全身动力学和氨基酸 (AA) 浓度保持稳定。胰高血糖素不仅增加了内脏对糖异生的摄取，而且还增加了必需氨基酸 (EAA) 的摄取，同时增加了它们从肌床的释放。基于区域示踪剂的动力学和 3-甲基组氨酸释放表明，肌肉中 EAA 的释放可能是由于蛋白质合成减少而不是蛋白质降解增加造成的。此外，许多已知影响胰岛素作用和代谢的代谢物因高胰高血糖素血症而改变，包括动脉血浆中亮氨酸和异亮氨酸的支链氨基酸和酮酸的增加。此外，注意到由于内脏床中赖氨酸的转化增加而导致α-氨基己二酸的动脉浓度增加。这些结果表明，低胰岛素血症期间的高胰高血糖素血症增加了净肌肉蛋白分解代谢，并显着增加了内脏和肌肉床之间的氨基代谢物交换。