Wise J K, Hendler R, Felig P
J Clin Invest. 1973 Nov;52(11):2774-82. doi: 10.1172/JCI107473.
Plasma concentrations of glucagon, insulin, glucose, and individual plasma amino acids were measured in normal nonobese and obese subjects before and after 3 days of dexamethasone treatment (2 mg/day) and in patients with Cushing's syndrome. The subjects were studied in the basal postabsorptive state and following the infusion of alanine (0.15 g/kg) or ingestion of a protein meal. In nonobese subjects dexamethasone treatment resulted in a 55% increment in basal glucagon levels and in a 60-100% increase in the maximal glucagon response to alanine infusion or protein ingestion. In obese subjects, basal glucagon rose by 110% following dexamethasone, while the response to alanine increased fourfold. In patients with Cushing's syndrome basal glucagon levels were 100% higher and the glucagon response to alanine infusion was 170% greater than in normal controls.Dexamethasone treatment in normal subjects resulted in a 40% rise in plasma alanine concentration which was directly proportional to the rise in basal glucagon. The remaining 14 amino acids were unchanged. In the patients with Cushing's syndrome alanine levels were 40% higher than in normal controls and were directly proportional to basal glucagon concentrations. No other plasma amino acids were significantly altered in the group with Cushing's syndrome. It is concluded that (a) glucocorticoids increase plasma glucagon concentration in the basal state and in response to protein ingestion or aminogenic stimulation; (b) this effect of glucocorticoids occurs in the face of obesity and persists in chronic hypercorticism; (c) hyperalaninemia is a characteristic of acute and chronic glucocorticoid excess, and may in turn contribute to steroid-induced hyperglucagonemia; and (d) increased alpha cell secretion may be a contributory factor in the gluconeogenic and diabetogenic effects of glucocorticoids.
在正常非肥胖和肥胖受试者中，于地塞米松治疗（2毫克/天）3天前后，以及在库欣综合征患者中，测量了胰高血糖素、胰岛素、葡萄糖和个体血浆氨基酸的血浆浓度。受试者在基础吸收后状态下以及输注丙氨酸（0.15克/千克）或摄入蛋白质餐后接受研究。在非肥胖受试者中，地塞米松治疗导致基础胰高血糖素水平增加55%，并且对丙氨酸输注或蛋白质摄入的最大胰高血糖素反应增加60 - 100%。在肥胖受试者中，地塞米松治疗后基础胰高血糖素升高了110%，而对丙氨酸的反应增加了四倍。在库欣综合征患者中，基础胰高血糖素水平比正常对照组高100%，并且对丙氨酸输注的胰高血糖素反应比正常对照组大170%。正常受试者接受地塞米松治疗后，血浆丙氨酸浓度升高了40%，这与基础胰高血糖素的升高成正比。其余14种氨基酸未发生变化。在库欣综合征患者中，丙氨酸水平比正常对照组高40%，并且与基础胰高血糖素浓度成正比。库欣综合征组中没有其他血浆氨基酸发生显著变化。得出的结论是：（a）糖皮质激素在基础状态下以及对蛋白质摄入或生氨刺激的反应中会增加血浆胰高血糖素浓度；（b）糖皮质激素的这种作用在肥胖情况下依然存在，并且在慢性皮质醇增多症中持续存在；（c）高丙氨酸血症是急性和慢性糖皮质激素过量的一个特征，并且可能反过来导致类固醇诱导的高胰高血糖素血症；（d）α细胞分泌增加可能是糖皮质激素的糖异生和致糖尿病作用的一个促成因素。
