Diabetes and Obesity Research Program, Garvan Institute of Medical Research, Sydney 2010, Australia.
J Nutr. 2011 Jul;141(7):1233-8. doi: 10.3945/jn.111.139824. Epub 2011 May 18.
Impaired glucagon-like peptide (GLP-1) secretion or response may contribute to ineffective insulin release in type 2 diabetes. The conditionally essential amino acid glutamine stimulates GLP-1 secretion in vitro and in vivo. In a randomized, crossover study, we evaluated the effect of oral glutamine, with or without sitagliptin (SIT), on postprandial glycemia and GLP-1 concentration in 15 type 2 diabetes patients (glycated hemoglobin 6.5 ± 0.6%). Participants ingested a low-fat meal (5% fat) after receiving either water (control), 30 g l-glutamine (Gln-30), 15 g L-glutamine (Gln-15), 100 mg SIT, or 100 mg SIT and 15 g L-glutamine (SIT+Gln-15). Studies were conducted 1-2 wk apart. Blood was collected at baseline and postprandially for 180 min for measurement of circulating glucose, insulin, C-peptide, glucagon, and total and active GLP-1. Gln-30 and SIT+Gln-15 reduced the early (t = 0-60 min) postprandial glycemic response compared with control. All Gln treatments enhanced the postprandial insulin response from t = 60-180 min but had no effect on the C-peptide response compared with control. The postprandial glucagon concentration was increased by Gln-30 and Gln-15 compared with control, but the insulin:glucagon ratio was not affected by any treatment. In contrast to Gln-30, which tended to increase the total GLP-1 AUC, SIT tended to decrease the total GLP-1 AUC relative to control (both P = 0.03). Gln-30 and SIT increased the active GLP-1 AUC compared with control (P = 0.008 and P = 0.01, respectively). In summary, Gln-30 decreased the early postprandial glucose response, enhanced late postprandial insulinemia, and augmented postprandial active GLP-1 responses compared with control. These findings suggest that glutamine may be a novel agent for stimulating GLP-1 concentration and limiting postprandial glycemia in type 2 diabetes.
胰高血糖素样肽 (GLP-1) 分泌或反应受损可能导致 2 型糖尿病患者胰岛素释放无效。条件必需氨基酸谷氨酰胺可刺激 GLP-1 在体外和体内的分泌。在一项随机交叉研究中,我们评估了口服谷氨酰胺(加或不加西他列汀[SIT])对 15 例 2 型糖尿病患者(糖化血红蛋白 6.5 ± 0.6%)餐后血糖和 GLP-1 浓度的影响。参与者在接受水(对照)、30 g L-谷氨酰胺(Gln-30)、15 g L-谷氨酰胺(Gln-15)、100 mg SIT 或 100 mg SIT 和 15 g L-谷氨酰胺(SIT+Gln-15)后摄入低脂肪餐(5%脂肪)。研究间隔 1-2 周进行。在基线和餐后 180 分钟采集血液,用于测量循环葡萄糖、胰岛素、C 肽、胰高血糖素以及总和活性 GLP-1。与对照相比,Gln-30 和 SIT+Gln-15 降低了早期(t = 0-60 分钟)餐后血糖反应。所有 Gln 处理均增强了从 t = 60-180 分钟的餐后胰岛素反应,但与对照相比,对 C 肽反应没有影响。与对照相比,Gln-30 和 Gln-15 增加了餐后胰高血糖素浓度,但胰岛素:胰高血糖素比值不受任何治疗影响。与 Gln-30 倾向于增加总 GLP-1 AUC 相反,SIT 倾向于降低总 GLP-1 AUC 与对照相比(两者 P = 0.03)。Gln-30 和 SIT 增加了与对照相比的活性 GLP-1 AUC(P = 0.008 和 P = 0.01)。总之,与对照相比,Gln-30 降低了早期餐后血糖反应,增强了晚期餐后胰岛素血症,并增强了餐后活性 GLP-1 反应。这些发现表明,谷氨酰胺可能是一种刺激 GLP-1 浓度和限制 2 型糖尿病餐后血糖的新型药物。