Paolisso G, Buonocore S, Gentile S, Sgambato S, Varricchio M, Scheen A, D'Onofrio F, Lefèbvre P J
Istituto di Gerontologia e Geriatria, 1st Medical School, University of Naples, Italy.
Diabetologia. 1990 May;33(5):272-7. doi: 10.1007/BF00403320.
The present study aimed at investigating the hyperglycaemic, lipolytic and ketogenic effects of small doses of glucagon delivered continuously or in a pulsatile manner. The study was performed in eight healthy young volunteers (24.2 +/- 1.2 years) and in eight healthy aged subjects (69.4 +/- 2.0 years). In all the subjects, endogenous pancreatic hormone secretion was inhibited by somatostatin and only glucagon was replaced. Consequently, the effects of pulsatile and continuous glucagon delivery were studied in conditions of progressive somatostatin-induced insulin deficiency. In both the young and the aged subjects, pulsatile glucagon delivery resulted in increases in plasma glucose, non-esterified fatty acid, glycerol and beta-hydroxybutyrate levels greater than those observed when the same amount of glucagon was delivered in a continuous manner. The net increases in plasma glucose, glycerol and non-esterified fatty acid levels were similar between the young and the aged subjects when glucagon was infused continuously; in contrast, the rise in plasma beta-hydroxybutyrate in the aged was only about half that observed in the young subjects. Surprisingly, when glucagon was infused in a pulsatile manner, the rises in plasma glycerol, non-esterified fatty acid and beta-hydroxybutyrate levels were all significantly smaller in the aged subjects, while no significant differences were observed in the blood glucose responses. We conclude that, in the presence of somatostatin-induced insulin deficiency, pulsatile glucagon exerts greater effects on blood glucose, plasma non-esterified fatty acid, glycerol and beta-hydroxybutyrate levels than its continuous delivery. In the elderly, the lipolytic and ketogenic, but not the hyperglycaemic, responses to pulsatile glucagon are significantly reduced.
本研究旨在探究以持续或脉冲方式给予小剂量胰高血糖素的高血糖、脂解和生酮作用。该研究在8名健康年轻志愿者（24.2±1.2岁）和8名健康老年受试者（69.4±2.0岁）中进行。在所有受试者中，生长抑素抑制内源性胰腺激素分泌，仅补充胰高血糖素。因此，在生长抑素诱导的胰岛素缺乏逐渐加重的情况下，研究了脉冲式和持续给予胰高血糖素的效果。在年轻和老年受试者中，脉冲式给予胰高血糖素导致血浆葡萄糖、非酯化脂肪酸、甘油和β-羟基丁酸水平的升高幅度大于以持续方式给予相同量胰高血糖素时观察到的升高幅度。当持续输注胰高血糖素时，年轻和老年受试者血浆葡萄糖、甘油和非酯化脂肪酸水平的净升高相似；相反，老年人血浆β-羟基丁酸的升高仅约为年轻受试者的一半。令人惊讶的是，当以脉冲方式输注胰高血糖素时，老年受试者血浆甘油、非酯化脂肪酸和β-羟基丁酸水平的升高均显著较小，而血糖反应未观察到显著差异。我们得出结论，在生长抑素诱导的胰岛素缺乏情况下，脉冲式胰高血糖素对血糖、血浆非酯化脂肪酸、甘油和β-羟基丁酸水平的影响大于其持续给药。在老年人中，对脉冲式胰高血糖素的脂解和生酮反应显著降低，但高血糖反应未降低。
