Pratipanawatr Thongchai, Pratipanawatr Wilailak, Rosen Clifford, Berria Rachele, Bajaj Mandeep, Cusi Kenneth, Mandarino Lawrence, Kashyap Sangeta, Belfort Renata, DeFronzo Ralph A
Diabetes Division, Department of Medicine, University of Texas Health Science Center, San Antonio, Texas 78229-3900, USA.
Am J Physiol Endocrinol Metab. 2002 Jun;282(6):E1360-8. doi: 10.1152/ajpendo.00335.2001.
The effects of insulin-like growth factor I (IGF-I) and insulin on free fatty acid (FFA) and glucose metabolism were compared in eight control and eight type 2 diabetic subjects, who received a two-step euglycemic hyperinsulinemic (0.25 and 0.5 mU x kg(-1) x min(-1)) clamp and a two-step euglycemic IGF-I (26 and 52 pmol x kg(-1) x min(-1)) clamp with [3-(3)H]glucose, [1-(14)C]palmitate, and indirect calorimetry. The insulin and IGF-I infusion rates were chosen to augment glucose disposal (R(d)) to a similar extent in control subjects. In type 2 diabetic subjects, stimulation of R(d) (second clamp step) in response to both insulin and IGF-I was reduced by approximately 40-50% compared with control subjects. In control subjects, insulin was more effective than IGF-I in suppressing endogenous glucose production (EGP) during both clamp steps. In type 2 diabetic subjects, insulin-mediated suppression of EGP was impaired, whereas EGP suppression by IGF-I was similar to that of controls. In both control and diabetic subjects, IGF-I-mediated suppression of plasma FFA concentration and inhibition of FFA turnover were markedly impaired compared with insulin (P < 0.01-0.001). During the second IGF-I clamp step, suppression of plasma FFA concentration and FFA turnover was impaired in diabetic vs. control subjects (P < 0.05-0.01).
在8名对照受试者和8名2型糖尿病受试者中比较了胰岛素样生长因子I（IGF-I）和胰岛素对游离脂肪酸（FFA）及葡萄糖代谢的影响，这些受试者接受了两步正常血糖高胰岛素血症（0.25和0.5 mU·kg⁻¹·min⁻¹）钳夹以及两步正常血糖IGF-I（26和52 pmol·kg⁻¹·min⁻¹）钳夹，并使用了[3-(³)H]葡萄糖、[1-(¹⁴)C]棕榈酸酯和间接测热法。胰岛素和IGF-I的输注速率选择为在对照受试者中使葡萄糖处置率（R(d)）增加到相似程度。在2型糖尿病受试者中，与对照受试者相比，胰岛素和IGF-I刺激的R(d)（第二步钳夹）降低了约40 - 50%。在对照受试者中，在两个钳夹步骤中胰岛素在抑制内源性葡萄糖生成（EGP）方面比IGF-I更有效。在2型糖尿病受试者中，胰岛素介导的EGP抑制受损，而IGF-I对EGP的抑制与对照相似。在对照和糖尿病受试者中，与胰岛素相比，IGF-I介导的血浆FFA浓度抑制和FFA周转抑制均明显受损（P < 0.01 - 0.001）。在第二个IGF-I钳夹步骤中，糖尿病受试者与对照受试者相比，血浆FFA浓度和FFA周转的抑制受损（P < 0.05 - 0.01）。
1）IGF-I在抑制EGP和FFA周转方面比胰岛素效果差；2）胰岛素抵抗的2型糖尿病受试者在骨骼肌中也表现出IGF-I抵抗。然而，IGF-I对糖尿病个体EGP的抑制未受损，表明肝脏对IGF-I敏感性正常。
