Meneilly G S, McIntosh C H, Pederson R A, Habener J F, Gingerich R, Egan J M, Finegood D T, Elahi D
Department of Medicine, University of British Columbia, Vancouver, Canada.
Diabetes Care. 2001 Nov;24(11):1951-6. doi: 10.2337/diacare.24.11.1951.
An important cause of elevated glucose levels in elderly patients with diabetes is an alteration in non-insulin-mediated glucose uptake (NIMGU). Glucagon-like peptide 1 (GLP-1) is an intestinal insulinotropic hormone. It has been proposed that this hormone also lowers glucose levels by enhancing NIMGU. This study was conducted to determine whether GLP-1 augments NIMGU in elderly patients with diabetes, a group in which NIMGU is known to be impaired. Studies were conducted on 10 elderly patients with type 2 diabetes (aged 75 +/- 2 years, BMI 27 +/- 1 kg/m(2)) who underwent paired 240-min glucose clamp studies. In each study, octreotide was infused to suppress endogenous insulin release, and tritiated glucose methodology was used to measure glucose production and disposal rates. For the first 180 min, no glucose was infused. From 180 to 240 min, glucose was increased to 11 mmol/l using the glucose clamp protocol. In the GLP-1 study, GLP-1 was infused from 30 to 240 min. In a subsequent control study, insulin was infused using the glucose clamp protocol from 30 to 240 min to match the insulin levels that occurred during the GLP-1 infusion study. During hyperglycemia, GLP-1 enhanced glucose disposal (control study: 2.52 +/- 0.19 mg x kg(-1) x min(-1); GLP-1 study: 2.90 +/- 0.17 mg x kg(-1) x min(-1); P < 0.0001). Hepatic glucose output was not different between studies. We conclude that GLP-1 may partially reverse the defect in NIMGU that occurs in elderly patients with diabetes.
老年糖尿病患者血糖水平升高的一个重要原因是非胰岛素介导的葡萄糖摄取（NIMGU）改变。胰高血糖素样肽1（GLP-1）是一种肠道促胰岛素激素。有人提出，这种激素还可通过增强NIMGU来降低血糖水平。本研究旨在确定GLP-1是否能增强老年糖尿病患者的NIMGU，已知该组患者的NIMGU受损。对10例老年2型糖尿病患者（年龄75±2岁，体重指数27±1kg/m²）进行了配对的240分钟葡萄糖钳夹研究。在每项研究中，输注奥曲肽以抑制内源性胰岛素释放，并使用氚标记葡萄糖方法测量葡萄糖生成和处置率。最初180分钟不输注葡萄糖。从180至240分钟，使用葡萄糖钳夹方案将葡萄糖浓度升至11mmol/l。在GLP-1研究中，从30至240分钟输注GLP-1。在随后的对照研究中，从30至240分钟使用葡萄糖钳夹方案输注胰岛素，使其胰岛素水平与GLP-1输注研究期间的胰岛素水平相匹配。在高血糖期间，GLP-1增强了葡萄糖处置（对照研究：2.52±0.19mg·kg⁻¹·min⁻¹；GLP-1研究：2.90±0.17mg·kg⁻¹·min⁻¹；P<0.0001）。两项研究之间肝脏葡萄糖输出无差异。我们得出结论，GLP-1可能部分逆转老年糖尿病患者中出现的NIMGU缺陷。
