Morrow G W, Kieffer T J, McIntosh C H, MacGillivray R T, Brown J C, St Pierre S, Pederson R A
Department of Physiology, University of British Columbia, Vancouver, Canada.
Can J Physiol Pharmacol. 1996 Jan;74(1):65-72.
Glucose-dependent insulinotropic polypeptide or gastric inhibitory polypeptide (GIP) is a 42 amino acid intestinal hormone, which exhibits several direct and indirect effects on fat and glucose metabolism. To determine the bioactive region(s) of the molecule, synthetic and proteolytic fragments of the hormone were generated and tested for their ability to induce a biological response in the isolated, perfused rat pancreas and stomach. A synthetic fragment corresponding to porcine GIP residues 1-30 retained strong insulinotropic activity in the isolated, perfused rat pancreas but greatly reduced somatostatinotropic activity in the isolated perfused rat stomach. A synthetic fragment corresponding to porcine GIP residues 15 to 30 was biologically inactive. However, enterokinase treatment of the synthetic 15-30 fragment restored partial insulinotropic activity in the isolated, perfused rat pancreas. The hypothesis that the restoration of biological activity was due to the enzymatic removal of the amino-terminal dipeptide (Asp-Lys) of GIP15-30 was supported by the observation that a synthetic fragment lacking these two residues was also insulinotropic. Further fractionation of the molecule generated a biologically active 19-30 fragment, suggesting that the residues necessary for the insulin response are contained within this region.
葡萄糖依赖性促胰岛素多肽或胃抑制多肽（GIP）是一种由42个氨基酸组成的肠激素，它对脂肪和葡萄糖代谢具有多种直接和间接作用。为了确定该分子的生物活性区域，制备了该激素的合成片段和蛋白水解片段，并检测它们在离体灌注大鼠胰腺和胃中诱导生物反应的能力。对应于猪GIP 1-30位残基的合成片段在离体灌注大鼠胰腺中保留了较强的促胰岛素活性，但在离体灌注大鼠胃中促生长抑素活性大大降低。对应于猪GIP 15-30位残基的合成片段无生物活性。然而，用肠激酶处理合成的15-30片段可恢复离体灌注大鼠胰腺中的部分促胰岛素活性。观察到缺少这两个残基的合成片段也具有促胰岛素作用，这支持了生物活性的恢复是由于酶促去除了GIP15-30的氨基末端二肽（天冬氨酸-赖氨酸）这一假说。对该分子进一步分级分离得到了具有生物活性的19-30片段，表明胰岛素反应所需的残基包含在该区域内。
