Oral glutamine increases circulating glucagon-like peptide 1, glucagon, and insulin concentrations in lean, obese, and type 2 diabetic subjects.
Oral glutamine increases circulating glucagon-like peptide 1, glucagon, and insulin concentrations in lean, obese, and type 2 diabetic subjects.
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DOI：
10.3945/ajcn.2008.26362
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发表时间：
2009-01
期刊：
影响因子：
--
通讯作者：
Gribble FM
中科院分区：
文献类型：
--
作者：
Greenfield JR;Farooqi IS;Keogh JM;Henning E;Habib AM;Blackwood A;Reimann F;Holst JJ;Gribble FM
胰升糖素激素，如胰升糖素样肽-1(GLP-1)和葡萄糖依赖的促胰岛素多肽(GIP)，在与膳食相关的胰岛素分泌中起着重要作用。我们先前证明，谷氨酰胺在体外对GLP-1的分泌有很强的刺激作用。以确定谷氨酰胺是否增加体内循环中的GLP-1和GIP水平，如果是，这是否与血浆胰岛素的增加有关。我们招募了8名健康、正常体重的志愿者(LEAN)、8名肥胖的2型糖尿病或糖耐量低减患者(OB-DIAB)和8名肥胖的非糖尿病对照组(OB-CON)。随机分3天口服葡萄糖(75g)、谷氨酰胺(30g)和水，测定血浆GLP-1、GIP、胰岛素、胰高血糖素和葡萄糖浓度。口服葡萄糖导致循环GLP-1水平升高，在LEAN组(31.9±5.7pmol/L)和OB-CON组(24.3±2.1pmol/L)在30min达到峰值，而OB-Diab组在45min(19.5±1.8pmol/L)达到峰值。谷氨酰胺摄入后，各研究组血浆GLP-1水平均升高，其中瘦型、CON和OB-Diab受试者在30min时的峰值分别为22.5±3.4pmo1/L、17.9±1.1pmo1/L和17.3±3.4pmo1/L。谷氨酰胺也能增加血浆GIP水平，但效果不如葡萄糖。与GLP-1和GIP的升高一致，谷氨酰胺显著增加循环血浆胰岛素水平。谷氨酰胺刺激了所有三个研究组的胰升糖素分泌。谷氨酰胺可有效提高体内循环GLP-1、GIP和胰岛素水平，并可能代表一种刺激肥胖症和2型糖尿病患者胰岛素分泌的新疗法。
Incretin hormones, such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), play an important role in meal-related insulin secretion. We previously demonstrated that glutamine is a potent stimulus of GLP-1 secretion in vitro. To determine whether glutamine increases circulating GLP-1 and GIP levels in vivo and, if so, whether this is associated with an increase in plasma insulin. We recruited 8 healthy, normal-weight volunteers (LEAN), 8 obese individuals with type 2 diabetes or impaired glucose tolerance (OB-DIAB) and 8 obese non-diabetic controls (OB-CON). Oral glucose (75g), glutamine (30g) and water were administered on three separate days in random order and plasma concentrations of GLP-1, GIP, insulin, glucagon and glucose were measured over 120 minutes. Oral glucose led to increases in circulating GLP-1 levels, peaking at 30 min in LEAN (31.9±5.7 pmol/L) and OB-CON (24.3±2.1 pmol/L) subjects and at 45 min in OB-DIAB subjects (19.5±1.8 pmol/L). Circulating GLP-1 levels increased in all study groups following glutamine ingestion, with peak levels at 30 min of 22.5±3.4 pmol/L, 17.9±1.1 pmol/L and 17.3±3.4 pmol/L in LEAN, OB-CON and OB-DIAB subjects, respectively. Glutamine also increased plasma GIP levels, but less effectively than glucose. Consistent with the increases in GLP-1 and GIP, glutamine significantly increased circulating plasma insulin levels. Glutamine stimulated glucagon secretion in all three study groups. Glutamine effectively increases circulating GLP-1, GIP and insulin levels in vivo and may represent a novel therapeutic approach to stimulating insulin secretion in obesity and type 2 diabetes.
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