Exogenous Glucose-Dependent Insulinotropic Polypeptide Worsens Postprandial Hyperglycemia in Type 2 Diabetes
Exogenous Glucose-Dependent Insulinotropic Polypeptide Worsens Postprandial Hyperglycemia in Type 2 Diabetes
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DOI：
10.2337/db08-0958
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发表时间：
2009-06-01
期刊：
影响因子：
7.7
通讯作者：
Egan, Josephine M.
中科院分区：
文献类型：
--
作者：
Chia, Chee W.;Carlson, Olga D.;Egan, Josephine M.
目的：与胰高血糖素样肽(GLP)-1不同，葡萄糖依赖性胰岛素性多肽（GIP）在2型糖尿病患者中缺乏降血糖特性。我们设计这项研究是为了阐明潜在的病理生理学。研究设计与方法：22例未接受胰岛素治疗的2型糖尿病患者分别给予人工合成GIP （20 ng）和人工合成GIP （20 ng）。公斤(1)。Min（-1）或安慰剂（生理盐水）超过180分钟，从第一口混合餐（加1g对乙酰氨基酚）开始，在两个不同的场合。在6小时内频繁采血，测定血浆GIP、GLP-1、葡萄糖、胰岛素、胰高血糖素、抵抗素和对乙酰氨基酚水平。结果：与安慰剂相比，GIP诱导早期餐后胰岛素水平升高。有趣的是，GIP还诱导餐后早期胰高血糖素升高，餐后晚期血糖显著升高，餐后晚期GLP-1水平降低。两种干预措施中抵抗素和对乙酰氨基酚水平相当。免疫细胞化学检测发现，GIP受体存在于人和小鼠的a细胞上。在α - TC1细胞系中，GIP诱导细胞内cAMP和胰高血糖素分泌增加。结论- gip在2型糖尿病患者中仍具有早期、短期的胰岛素促胰岛素作用。然而，随着胰高血糖素的增加，降低血糖的效果就消失了。GIP输注进一步加重餐后高血糖，很可能是通过其对GLP-1的抑制作用。这些发现使得GIP或GIP受体激动剂不太可能用于治疗2型糖尿病患者的高血糖。糖尿病杂志，2009
OBJECTIVE-Glucose-dependent insulinotropic polypeptide (GIP), unlike glucagon-like peptide (GLP)-1, lacks glucose-lowering properties in patients with type 2 diabetes. We designed this study to elucidate the underlying pathophysiology.RESEARCH DESIGN AND METHODS-Twenty-two insulin-naive subjects with type 2 diabetes were given either synthetic human GIP (20 ng . kg(-1) . min(-1)) or placebo (normal saline) over 180 min, starting with the first bite of a mixed meal (plus 1 g of acetaminophen) on two separate occasions. Frequent blood samples were obtained over 6 h to determine plasma GIP, GLP-1, glucose, insulin, glucagon, resistin, and acetaminophen levels.RESULTS-Compared with placebo, GIP induced an early postprandial increase in insulin levels. Intriguingly, GIP also induced an early postprandial augmentation in glucagon, a significant elevation in late postprandial glucose, and a decrease in late postprandial GLP-1 levels. Resistin and acetaminophen levels were comparable in both interventions. By immunocytochemistry, GIP receptors were present on human and mouse a-cells. In alpha TC1 cell line, GIP induced an increase in intracellular cAMP and glucagon secretion.CONCLUSIONS-GIP, given to achieve supraphysiological plasma levels, still had an early, short-lived insulinotropic effect in type 2 diabetes. However, with a concomitant increase in glucagon, the glucose-lowering effect was lost. GIP infusion further worsened hyperglycemia postprandially, most likely through its suppressive effect on GLP-1. These findings make it unlikely that GIP or GIP receptor agonists will be useful in treating the hyperglycemia of patients with type 2 diabetes. Diabetes 58:1342-1349, 2009