School of Biomedical Sciences, SAAD Centre for Pharmacy and Diabetes, University of Ulster, Coleraine BT52 1SA, UK.
J Endocrinol. 2011 Mar;208(3):265-71. doi: 10.1530/JOE-10-0419. Epub 2011 Jan 6.
Glucose-dependent insulinotropic polypeptide (GIP) is a 42 amino acid hormone secreted from intestinal K-cells, which exhibits a number of actions including stimulation of insulin release. A truncated form, GIP(1-30), has recently been demonstrated in intestine and islet α-cells. To evaluate the potential physiological significance of this naturally occurring form of GIP, the present study has examined and compared the bioactivity of enzymatically stabilised forms, [D-Ala²]GIP(1-30) and [D-Ala²]GIP(1-42), in high-fat fed mice. Twice-daily injection of GIP peptides for 42 days had no significant effect on food intake or body weight. However, non-fasting glucose levels were significantly lowered, and insulin levels were elevated in both treatment groups compared to saline controls. The glycaemic response to i.p. glucose was correspondingly improved (P < 0.05) in [D-Ala²]GIP(1-30)- and [D-Ala²]GIP(1-42)-treated mice. Furthermore, glucose-stimulated plasma insulin levels were significantly elevated in both treatment groups compared to control mice. Insulin sensitivity was not significantly different between any of the groups. Similarly, plasma lipid profile, O₂ consumption, CO₂ production, respiratory exchange ratio, and energy expenditure were not altered by 42 days twice-daily treatment with [D-Ala²]GIP(1-30) or [D-Ala²]GIP(1-42). In contrast, ambulatory activity was significantly (P < 0.05) elevated during the light phase in both GIP treatment groups compared to saline controls. The results reveal that sustained GIP receptor activation exerts a spectrum of beneficial metabolic effects in high-fat fed mice. However, no differences were discernable between the biological actions of the enzyme-resistant analogues of the naturally occurring forms, GIP(1-30) and GIP(1-42).
葡萄糖依赖性胰岛素多肽（GIP）是一种 42 个氨基酸的激素，从肠道 K 细胞分泌，具有刺激胰岛素释放等多种作用。最近在肠道和胰岛α细胞中发现了一种截断形式，GIP（1-30）。为了评估这种天然存在形式的 GIP 的潜在生理意义，本研究比较了两种酶稳定形式的生物活性，[D-Ala2]GIP（1-30）和[D-Ala2]GIP（1-42），在高脂肪喂养的小鼠中。GIP 肽每天两次注射 42 天对食物摄入量或体重没有显著影响。然而，与盐水对照组相比，非禁食状态下的血糖水平显著降低，胰岛素水平升高。[D-Ala2]GIP（1-30）和[D-Ala2]GIP（1-42）治疗组的血糖反应也相应改善（P<0.05）。此外，与对照组相比，两组治疗组的葡萄糖刺激的血浆胰岛素水平均显著升高。各组之间的胰岛素敏感性没有显著差异。同样，42 天每天两次用[D-Ala2]GIP（1-30）或[D-Ala2]GIP（1-42）治疗不会改变血浆脂质谱、O2 消耗、CO2 产生、呼吸交换率和能量消耗。相反，在 GIP 治疗组中，活动量在光照期显著增加（P<0.05），与盐水对照组相比。结果表明，持续的 GIP 受体激活在高脂肪喂养的小鼠中发挥了一系列有益的代谢作用。然而，天然存在形式的 GIP（1-30）和 GIP（1-42）的酶抗性类似物的生物学作用没有差异。
