Meneilly G S, McIntosh C H, Pederson R A, Habener J F, Gingerich R, Egan J M, Elahi D
Department of Medicine, University of British Columbia, Vancouver, Canada.
J Gerontol A Biol Sci Med Sci. 2001 Nov;56(11):M681-5. doi: 10.1093/gerona/56.11.m681.
Glucagon-like peptide-1 (GLP-1) is an intestinal insulinotropic hormone that augments glucose-induced insulin secretion in patients with type 2 diabetes. It has also been proposed that a substantial component of the glucose-lowering effects of GLP-1 occurs because this hormone enhances insulin-mediated glucose disposal. However, interpretations of the studies have been controversial. This study determines the effect of GLP-1 on insulin-mediated glucose disposal in elderly patients with type 2 diabetes.
Studies were conducted on 8 elderly patients with type 2 diabetes (age range, 76 +/- 1 years; body mass index, 28 +/- 1 kg/m(2)). Each subject underwent two 180-minute euglycemic (insulin infusion rate, 40 mU/m(2)/min) insulin clamps in random order. Glucose production (Ra) and disposal (Rd) rates were measured using tritiated glucose methodology. In one study, glucose and insulin alone were infused. In the other study, a primed-continuous infusion of GLP-1 was administered at a final rate of 1.5 pmol x kg(-1) x min(-1) from 30 to 180 minutes.
Glucose values were similar between the control and GLP-1 infusion studies. 120- to 180-minute insulin values appeared to be higher during the GLP-1 infusion study (control, 795 +/- 63 pmol/l; GLP-1, 1140 +/- 275 pmol/l; p = not significant [NS]). The higher insulin values were largely due to 2 subjects who had substantial insulin responses to GLP-1 despite euglycemia and hyperinsulinemia. The 120- to 180-minute insulin values were similar in the other 6 subjects (control, 746 +/- 35 pmol/l; GLP-1, 781 +/- 41 pmol/l; p = NS). Basal (control, 2.08 +/- 0.05 mg/kg/min; GLP-1, 2.13 +/- 0.04 mg/kg/min; p = NS) and 120- to 180-minute (control, 0.50 +/- 0.18 mg/kg/min; GLP-1, 0.45 +/- 0.14 mg/kg/min; p = NS) Ra was similar between studies. The 120- to 180-minute Rd values were higher during the GLP-1 infusion studies (control, 4.73 +/- 0.39 mg/kg/min; GLP-1, 5.52 +/- 0.43 mg/kg/min; p <.01). When the 2 subjects who had significant insulin responses to GLP-1 during the euglycemic clamp were excluded, the 120- to 180-minute Rd values were still higher in the GLP-1 infusion study (control, 5.22 +/- 0.32 mg/kg/min; GLP-1, 6.05 +/- 0.37 mg/kg/min; p <.05).
We conclude that GLP-1 may enhance insulin sensitivity in elderly patients with diabetes.
胰高血糖素样肽-1（GLP-1）是一种肠道促胰岛素激素，可增强2型糖尿病患者葡萄糖诱导的胰岛素分泌。也有人提出，GLP-1降血糖作用的一个重要组成部分是因为这种激素增强了胰岛素介导的葡萄糖代谢。然而，对这些研究的解释一直存在争议。本研究确定GLP-1对老年2型糖尿病患者胰岛素介导的葡萄糖代谢的影响。
对8例老年2型糖尿病患者（年龄范围76±1岁；体重指数28±1kg/m²）进行研究。每位受试者随机接受两次180分钟的正常血糖（胰岛素输注速率40mU/m²/min）胰岛素钳夹试验。使用氚标记葡萄糖方法测量葡萄糖生成（Ra）和代谢（Rd）速率。在一项研究中，仅输注葡萄糖和胰岛素。在另一项研究中，从30分钟至180分钟以1.5pmol·kg⁻¹·min⁻¹的最终速率进行GLP-1的首剂-持续输注。
对照研究和GLP-1输注研究中的葡萄糖值相似。在GLP-1输注研究期间，120至180分钟的胰岛素值似乎更高（对照，795±63pmol/L；GLP-1，1140±275pmol/L；p=无显著差异[NS]）。较高的胰岛素值主要归因于2名受试者，尽管处于正常血糖和高胰岛素血症状态，但他们对GLP-1有显著的胰岛素反应。其他6名受试者120至180分钟的胰岛素值相似（对照，746±35pmol/L；GLP-1，781±41pmol/L；p=NS）。两项研究之间的基础（对照，2.08±0.05mg/kg/min；GLP-1，2.13±0.04mg/kg/min；p=NS）和120至180分钟（对照，0.50±0.18mg/kg/min；GLP-1，0.45±0.14mg/kg/min；p=NS）的Ra相似。在GLP-1输注研究期间，120至180分钟的Rd值更高（对照，4.73±0.39mg/kg/min；GLP-1，5.52±0.43mg/kg/min；p<.01）。当排除在正常血糖钳夹期间对GLP-1有显著胰岛素反应的2名受试者时，GLP-1输注研究中120至180分钟的Rd值仍然更高（对照，5.22±0.32mg/kg/min；GLP-1，6.05±0.37mg/kg/min；p<.05）。
我们得出结论，GLP-1可能增强老年糖尿病患者的胰岛素敏感性。
