McCall R H, Wiesenthal S R, Shi Z Q, Polonsky K, Giacca A
Department of Physiology, Medicine, and Surgery, University of Toronto, Ontario Canada.
Am J Physiol. 1998 Feb;274(2):E346-56. doi: 10.1152/ajpendo.1998.274.2.E346.
To determine whether the predominant effect of insulin in suppressing tracer-determined glucose production (Ra) is hepatic or peripheral, we infused insulin peripherally (PER) and portally (POR) at both low (0.75 pmol.kg-1.min-1) and high physiological rates (2.7 pmol.kg-1.min-1) during euglycemic clamps in normal dogs. We also infused insulin peripherally at one-half these rates (1/2 PER) to match the peripheral insulin levels in POR and thus obtain a selective POR vs. 1/2 PER difference in hepatic insulin levels. At the high-rate insulin infusion, peripheral insulin levels were greatest with PER (PER = 212 +/- 10 pM, n = 5; POR = 119 +/- 5 pM, n = 6; 1/2 PER = 122 +/- 5 pM, n = 6). Calculated hepatic insulin levels were greatest with POR (POR = 227 +/- 13 pM, PER = 206 +/- 19 pM, 1/2 PER = 123 +/- 8 pM). High-dose PER yielded a greater suppression of Ra than POR (79 +/- 18 vs. 56 +/- 6%, P < .001). Ra was only suppressed by 45 +/- 6% with 1/2 PER (P < 0.01 vs. POR on 6 paired experiments). Free fatty acid (FFA) was suppressed by 57 +/- 8% with PER and only by 33 +/- 5 and 37 +/- 2% with POR and 1/2 PER, respectively. The low-dose PER and POR yielded an equal Ra suppression (PER = 46 +/- 9%, POR = 43 +/- 4%). Only 1/2 PER was associated with a lower suppression of Ra (36 +/- 8, P < 0.05 vs. POR). FFA showed similar suppression in all three groups (approximately 25%). Using both insulin infusion rates, the percent Ra suppression per unit difference in peripheral insulin was approximately twofold greater than that per unit difference in hepatic insulin. These results suggest that, during euglycemic clamps without somatostatin in normal dogs, Ra suppression is mediated by both peripheral and hepatic effects of insulin and that peripheral insulin, at least at high physiological infusion rates, is more potent than hepatic insulin in suppressing Ra.
为了确定胰岛素抑制示踪剂测定的葡萄糖生成率（Ra）的主要作用是在肝脏还是外周，我们在正常犬的正常血糖钳夹期间，以低（0.75 pmol·kg⁻¹·min⁻¹）和高生理速率（2.7 pmol·kg⁻¹·min⁻¹）分别经外周（PER）和门静脉（POR）输注胰岛素。我们还以这些速率的一半经外周输注胰岛素（1/2 PER），以匹配POR组的外周胰岛素水平，从而获得肝脏胰岛素水平上POR与1/2 PER的选择性差异。在高剂量胰岛素输注时，PER组的外周胰岛素水平最高（PER = 212 ± 10 pM，n = 5；POR = 119 ± 5 pM，n = 6；1/2 PER = 122 ± 5 pM，n = 6）。计算得出POR组的肝脏胰岛素水平最高（POR = 227 ± 13 pM，PER = 206 ± 19 pM，1/2 PER = 123 ± 8 pM）。高剂量PER对Ra的抑制作用大于POR（79 ± 18% 对 56 ± 6%，P < 0.001）。1/2 PER对Ra的抑制仅为45 ± 6%（在6对实验中，与POR相比P < 0.01）。PER使游离脂肪酸（FFA）降低57 ± 8%，而POR和1/2 PER分别仅使其降低33 ± 5%和37 ± 2%。低剂量PER和POR对Ra的抑制作用相同（PER = 46 ± 9%，POR = 43 ± 4%）。只有1/2 PER对Ra的抑制作用较低（36 ± 8%，与POR相比P < 0.05）。FFA在所有三组中的降低情况相似（约25%）。使用两种胰岛素输注速率时，外周胰岛素每单位差异引起的Ra抑制百分比比肝脏胰岛素每单位差异引起的约大两倍。这些结果表明，在正常犬无生长抑素的正常血糖钳夹期间，Ra的抑制是由胰岛素的外周和肝脏作用共同介导的，并且外周胰岛素至少在高生理输注速率下，在抑制Ra方面比肝脏胰岛素更有效。
