Hvidberg A, Nielsen M T, Hilsted J, Orskov C, Holst J J
Department of Endocrinology, Hvidovre Hospital, Copenhagen, Denmark.
Metabolism. 1994 Jan;43(1):104-8. doi: 10.1016/0026-0495(94)90164-3.
The newly discovered intestinal hormone, glucagon-like peptide-1 (GLP-1) (proglucagon 78-107amide), stimulates insulin secretion and inhibits glucagon secretion in man and may therefore be anticipated to influence hepatic glucose production. To study this, we infused synthetic GLP-1 sequentially at rates of 25 and 75 pmol.kg-1.h-1 into eight healthy volunteers after an overnight fast and measured plasma concentrations of glucose, insulin, and glucagon and glucose turnover by a technique involving infusion of 3-3H-glucose. Plasma levels of GLP-1 increased by 21.3 +/- 3.1 and 75.4 +/- 3.2 pmol/L during the infusion, changes that were within physiologic limits. In a control experiment only saline was infused. During GLP-1 infusion, plasma glucose level decreased significantly (from 5.3 +/- 0.1 to 4.7 +/- 0.1 and 4.3 +/- 0.1 pmol/L at the end of the two infusion periods). Despite this, plasma insulin level increased significantly (from 20.5 +/- 2.9 to a peak value of 33.5 +/- 5.2 pmol/L during the second period), and plasma glucagon level decreased (from 9.3 +/- 1.7 to 7.1 +/- 1.0 pmol/L). Glucose rate of appearance (Ra) decreased significantly to 75% +/- 6% of the preinfusion values during GLP-1 infusion. Glucose disappearance rate (Rd) did not change significantly, but glucose clearance increased significantly compared with saline. All parameters of glucose turnover remained constant during saline infusion. We conclude that GLP-1 may potently control hepatic glucose production and glucose clearance through its effects on the pancreatic glucoregulatory hormones. The effect of GLP-1 on glucose production is consistent with its proposed use in the treatment of type II diabetes.
新发现的肠促胰素——胰高血糖素样肽-1（GLP-1）（胰高血糖素原78-107酰胺），可刺激人体胰岛素分泌并抑制胰高血糖素分泌，因此有望影响肝脏葡萄糖生成。为研究此作用，我们在8名健康志愿者禁食过夜后，以25和75 pmol·kg⁻¹·h⁻¹的速率依次静脉输注合成GLP-1，并通过输注³-³H-葡萄糖的技术测定血浆葡萄糖、胰岛素、胰高血糖素浓度及葡萄糖代谢率。输注期间，血浆GLP-1水平分别升高21.3±3.1和75.4±3.2 pmol/L，此变化处于生理范围内。在对照实验中仅输注生理盐水。输注GLP-1期间，血浆葡萄糖水平显著下降（两个输注期结束时分别从5.3±0.1降至4.7±0.1和4.3±0.1 pmol/L）。尽管如此，血浆胰岛素水平显著升高（第二期从20.5±2.9升至峰值33.5±5.2 pmol/L），血浆胰高血糖素水平下降（从9.3±1.7降至7.1±1.0 pmol/L）。GLP-1输注期间，葡萄糖出现率（Ra）显著降至输注前值的75%±6%。葡萄糖消失率（Rd）无显著变化，但与输注生理盐水相比，葡萄糖清除率显著增加。输注生理盐水期间，葡萄糖代谢的所有参数均保持恒定。我们得出结论，GLP-1可能通过对胰腺糖调节激素的作用有效控制肝脏葡萄糖生成和葡萄糖清除。GLP-1对葡萄糖生成的作用与其在2型糖尿病治疗中的应用设想相符。
