Comparison of sub-chronic metabolic effects of stable forms of naturally occurring GIP(1-30) and GIP(1-42) in high-fat fed mice
Comparison of sub-chronic metabolic effects of stable forms of naturally occurring GIP(1-30) and GIP(1-42) in high-fat fed mice
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DOI：
10.1530/joe-10-0419
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发表时间：
2011-03-01
影响因子：
4
通讯作者：
Flatt, Peter R.
中科院分区：
文献类型：
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作者：
Gault, Victor A.;Porter, David W.;Flatt, Peter R.
葡萄糖依赖性促胰岛素多肽（GIP）是由肠K细胞分泌的42个氨基酸的激素，其表现出包括刺激胰岛素释放的许多作用。截短形式GIP（1-30）最近已在肠和胰岛α细胞中得到证实。为了评估这种天然存在形式的GIP的潜在生理意义，本研究已经检查并比较了酶稳定形式[D-Ala（2）]-GIP（1-30）和[D-Ala（2）]GIP（1-42）在高脂肪喂养小鼠中的生物活性。每天两次注射GIP肽，持续42天，对食物摄入量或体重没有显著影响。然而，与生理盐水对照组相比，两个治疗组的非空腹血糖水平显著降低，胰岛素水平升高。[D-Ala（2）]GIP（1-30）和[D-Ala（2）] GIP（1-42）处理的小鼠对腹膜内葡萄糖的血液反应相应地改善（P < 0.05）。此外，与对照小鼠相比，两个给药组中葡萄糖刺激的血浆胰岛素水平显著升高。胰岛素敏感性在任何组之间均无显著差异。同样，每日两次给予[D-Ala（2）]GIP（1-30）或[D-Ala（2）] GIP（1-42）42天后，血浆脂质谱、O-2消耗量、CO2产生量、呼吸交换率和能量消耗均未发生改变。相比之下，与盐水对照相比，两个GIP治疗组中的活动在光相期间显著（P < 0.05）升高。结果表明，持续的GIP受体激活在高脂喂养的小鼠中发挥了一系列有益的代谢作用。然而，在天然存在形式的酶抗性类似物GIP（1-30）和GIP（1-42）的生物学作用之间没有可辨别的差异。内分泌学杂志（2011）208，265-271
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 alpha-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-Ala(2)]-GIP(1-30) and [D-Ala(2)]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-Ala(2)]GIP(1-30)- and [D-Ala(2)]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, O-2 consumption, CO2 production, respiratory exchange ratio, and energy expenditure were not altered by 42 days twice-daily treatment with [D-Ala(2)]GIP(1-30) or [D-Ala(2)]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). Journal of Endocrinology (2011) 208, 265-271