Lewis G F, Vranic M, Giacca A
Department of Medicine, University of Toronto, Ontario, Canada.
Am J Physiol. 1997 Mar;272(3 Pt 1):E371-8. doi: 10.1152/ajpendo.1997.272.3.E371.
The present study examines the role of glucagon in modulating the hepatic and extrahepatic effects of insulin on hepatic glucose production (HGP). We infused glucagon at a constant rate (0.65 ng x kg(-1) x min(-1)) during equimolar portal and peripheral insulin delivery in seven healthy males by our previously published tolbutamide infusion method. In contrast to our previous study, in which glucagon fell by approximately 30% during hyperinsulinemia and suppression of HGP was significantly greater with equimolar peripheral than with portal insulin delivery, HGP was actually suppressed to a lesser extent with peripheral insulin delivery (69 +/- 10%) than when insulin was delivered portally (76 +/- 5%, P < 0.05). To further examine whether glucagon was enhancing the effect of portal insulin, in four additional individuals HGP was suppressed to a greater extent during a tolbutamide infusion when glucagon was administered continuously throughout the basal and hyperinsulinemic periods than when glucagon was infused during the basal period only; HGP suppressed by 63 +/- 3 vs. 52 +/- 3%, respectively, P = 0.02). Tolbutamide had no effect on HGP when infused into three C-peptide-negative individuals with type I diabetes during a low-dose insulin and glucagon infusion. These data suggest that glucagon levels are an important determinant of the balance between insulin's direct and indirect effects on HGP, with glucagon likely potentiating the direct hepatic effect of insulin.
本研究探讨了胰高血糖素在调节胰岛素对肝葡萄糖生成（HGP）的肝脏和肝外作用中的作用。我们通过先前发表的甲苯磺丁脲输注方法，在7名健康男性等摩尔门静脉和外周胰岛素输注期间，以恒定速率（0.65 ng·kg⁻¹·min⁻¹）输注胰高血糖素。与我们之前的研究不同，在之前的研究中，高胰岛素血症期间胰高血糖素下降约30%，且等摩尔外周胰岛素输注比门静脉胰岛素输注对HGP的抑制作用明显更大，而此次研究中，外周胰岛素输注时HGP的抑制程度（69±10%）实际上低于门静脉输注胰岛素时（76±5%，P<0.05）。为了进一步研究胰高血糖素是否增强了门静脉胰岛素的作用，在另外4名个体中，与仅在基础期输注胰高血糖素相比，在基础期和高胰岛素血症期持续输注胰高血糖素时，甲苯磺丁脲输注期间HGP的抑制程度更大；HGP分别被抑制63±3%和52±3%，P = 0.02）。在低剂量胰岛素和胰高血糖素输注期间，将甲苯磺丁脲输注到3名I型糖尿病C肽阴性个体中时，甲苯磺丁脲对HGP没有影响。这些数据表明，胰高血糖素水平是胰岛素对HGP直接和间接作用平衡的重要决定因素，胰高血糖素可能增强胰岛素对肝脏的直接作用。
