Rennert N J, Caprio S, Sherwin R S
Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut.
J Clin Endocrinol Metab. 1993 Mar;76(3):804-6. doi: 10.1210/jcem.76.3.8445040.
The effect of human recombinant insulin-like growth factor I (rhIGF-1) on glucose stimulated insulin secretion was studied in 14 healthy human volunteers. Each subject received a primed-continuous infusion of rhIGF-1 (20 micrograms kg prime, 0.4 micrograms kg-1 min-1) or saline while plasma glucose was raised +2.8 mmol/l (+50 mg/dl) (n = 6) or +7.0 mmol/l (+125 mg/dl) (n = 8) above baseline for 2 h using the hyperglycemic clamp technique. Total IGF-1 levels during the IGF-1 studies increased from 196 +/- 37 to 449 +/- 71 ng/ml. At the +2.8 mmol/l (+50 mg/dl) stimulus, first and second phase C-peptide levels were suppressed during IGF-1 infusion vs control (885 +/- 157 vs 544 +/- 99 pmol/l, p < 0.05 and 1379 +/- 246 vs 832 +/- 130 pmol/l, p < 0.05, respectively), whereas insulin levels were suppressed during the second phase only (215 +/- 43 vs 151 +/- 28 pmol/l, p < 0.05). Despite this, the rate of glucose metabolism was two-fold higher in the IGF-1 infused group (8.0 +/- 0.5 vs 3.5 +/- 0.1 mg kg-1 min-1, p < 0.01). At the higher glucose stimulus +7.0 mmol/l (+125 mg/dl) only second phase C-peptide levels were significantly reduced (1922 +/- 251 vs 1466 +/- 74 pmol/l, p < 0.05). Again, rates of glucose metabolism were higher during IGF-1 infusion (11.8 +/- 1.2 vs 8.9 +/- 0.8 mg kg-1 min-1, p < 0.01). These data suggest that rhIGF-1 inhibits glucose-stimulated insulin secretion in humans, but that this inhibitory effect is partially overcome by increasing the hyperglycemic stimulus. Moreover, despite the decrease in insulin secretion, glucose disposal is accelerated by rhIGF-1.
在14名健康人类志愿者中研究了重组人胰岛素样生长因子I（rhIGF-1）对葡萄糖刺激的胰岛素分泌的影响。使用高血糖钳夹技术，在将血浆葡萄糖浓度升高至高于基线水平+2.8 mmol/l（+50 mg/dl）（n = 6）或+7.0 mmol/l（+125 mg/dl）（n = 8）并持续2小时的过程中，每名受试者接受rhIGF-1的首剂-持续输注（首剂20微克/千克，0.4微克/千克-1·分钟-1）或生理盐水输注。在rhIGF-1研究期间，总IGF-1水平从196±37 ng/ml升高至449±71 ng/ml。在+2.8 mmol/l（+50 mg/dl）刺激下，与对照组相比，在输注IGF-1期间，第一相和第二相C肽水平受到抑制（分别为885±157对544±99 pmol/l，p<0.05；1379±246对832±130 pmol/l，p<0.05），而仅在第二相胰岛素水平受到抑制（215±43对151±28 pmol/l，p<0.05）。尽管如此，输注IGF-1组的葡萄糖代谢率高出两倍（8.0±0.5对3.5±0.1毫克/千克-1·分钟-1，p<0.01）。在较高的葡萄糖刺激+7.0 mmol/l（+125 mg/dl）下，仅第二相C肽水平显著降低（1922±251对1466±74 pmol/l，p<0.05）。同样，在输注IGF-1期间葡萄糖代谢率更高（11.8±1.2对8.9±0.8毫克/千克-1·分钟-1，p<0.01）。这些数据表明，rhIGF-1抑制人类葡萄糖刺激的胰岛素分泌，但通过增加高血糖刺激可部分克服这种抑制作用。此外，尽管胰岛素分泌减少，但rhIGF-1可加速葡萄糖的处置。
