The Gluco- and Liporegulatory and Vasodilatory Effects of Glucose-Dependent Insulinotropic Polypeptide (GIP) Are Abolished by an Antagonist of the Human GIP Receptor
The Gluco- and Liporegulatory and Vasodilatory Effects of Glucose-Dependent Insulinotropic Polypeptide (GIP) Are Abolished by an Antagonist of the Human GIP Receptor
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DOI：
10.2337/db17-0480
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发表时间：
2017-09-01
期刊：
影响因子：
7.7
通讯作者：
Bulow, Jens
中科院分区：
文献类型：
--
作者：
Asmar, Meena;Asmar, Ali;Bulow, Jens
人类葡萄糖依赖性胰岛素性多肽（GIP）的截断形式，GIP(3-30) NH2，最近被确定为人类GIP受体的拮抗剂。本研究检测了GIP(3-30) NH2在人体葡萄糖代谢、皮下腹腔脂肪组织血流量（ATBF）和脂质代谢中拮抗GIP生理作用的能力。在高血糖-高胰岛素钳夹期间，同时输注GIP、GIP(3-30) NH2或同时输注GIP和GIP(3-30) NH2，通过测量动静脉代谢物浓度和ATBF，研究了8名瘦人。单独注射GIP(3-30) NH2和联合注射GIP时，胰岛素水平和为维持钳位而注射的总葡萄糖量低于单独注射GIP时。此外，在使用拮抗剂期间，ATBF保持不变，仅在与GIP联合使用时略有增加，而在单独使用GIP时，ATBF增加了5倍。在单独使用拮抗剂和联合使用GIP期间，脂肪组织甘油三酯（TAG）和葡萄糖摄取减少，游离脂肪酸/甘油比率增加。葡萄糖输注速率和血浆胰岛素水平的变化表明拮抗剂对GIP的肠促胰岛素作用有抑制作用。此外，拮抗剂抑制GIP诱导的ATBF增加，降低脂肪组织TAG摄取，表明GIP在脂质代谢中也起着至关重要的作用。
A truncated form of human glucose-dependent insulinotropic polypeptide (GIP), GIP(3-30) NH2, was recently identified as an antagonist of the human GIP receptor. This study examined the ability of GIP(3-30) NH2 to antagonize the physiological actions of GIP in glucose metabolism, subcutaneous abdominal adipose tissue blood flow (ATBF), and lipid metabolism in humans. Eight lean subjects were studied by measuring arteriovenous concentrations ofmetabolites and ATBF on three different occasions during hyperglycemic-hyperinsulinemic clamps with concomitant infusions of GIP, GIP(3-30) NH2, or both GIP and GIP(3-30) NH2. During infusion of GIP(3-30) NH2 alone and in combination with GIP, insulin levels and the total glucose amount infused to maintain the clamp were lower than during GIP alone. In addition, ATBF remained constant during the antagonist and increased only slightly in combination with GIP, whereas it increased fivefold during GIP alone. Adipose tissue triacylglyceride (TAG) and glucose uptake decreased, and the free fatty acid/glycerol ratio increased during the antagonist alone and in combination with GIP. The changes in glucose infusion rates and plasma insulin levels demonstrate an inhibitory effect of the antagonist on the incretin effect of GIP. In addition, the antagonist inhibited GIP-induced increase in ATBF and decreased the adipose tissue TAG uptake, indicating that GIP also plays a crucial role in lipid metabolism.