Department of Cellular and Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, Canada.
Am J Physiol Gastrointest Liver Physiol. 2010 May;298(5):G608-14. doi: 10.1152/ajpgi.00024.2010. Epub 2010 Feb 25.
Glucose-dependent insulinotropic polypeptide (GIP) is a hormone released from enteroendocrine K cells in response to meals. Posttranslational processing of the precursor protein pro-GIP at residue 65 by proprotein convertase subtilisin/kexin type 1 (PC1/3) in gut K cells gives rise to the established 42-amino-acid form of GIP (GIP(1-42)). However, the pro-GIP peptide sequence contains a consensus cleavage site for PC2 at residues 52-55 and we identified PC2 immunoreactivity in a subset of K cells, suggesting the potential existence of a COOH-terminal truncated GIP isoform, GIP(1-30). Indeed a subset of mouse and human K cells display GIP immunoreactivity with GIP antibodies directed to the mid portion of the peptide, but not with a COOH-terminal-directed GIP antibody, indicative of the presence of a truncated form of GIP. This population of cells represents approximately 5-15% of the total GIP-immunoreactive cells in mice, depending on the region of intestine, and is virtually absent in mice lacking PC2. Amidated GIP(1-30) and GIP(1-42) have comparable potency at stimulating somatostatin release in the perfused mouse stomach. Therefore, GIP(1-30) represents a naturally occurring, biologically active form of GIP.
葡萄糖依赖性胰岛素多肽 (GIP) 是一种激素，在进食后从肠内分泌 K 细胞中释放出来。前体蛋白 pro-GIP 在肠道 K 细胞中由蛋白原转化酶枯草溶菌素/激肽释放酶 1/3 (PC1/3) 在残基 65 处进行翻译后加工，产生已建立的 42 个氨基酸形式的 GIP(GIP(1-42))。然而，pro-GIP 肽序列在残基 52-55 处含有 PC2 的共识切割位点，并且我们在 K 细胞的亚群中鉴定出 PC2 免疫反应性，表明存在 COOH-末端截断的 GIP 同工型，GIP(1-30)。事实上，亚群的小鼠和人类 K 细胞显示出与 GIP 抗体的 GIP 免疫反应性，该抗体针对肽的中部，但不与 COOH-末端定向的 GIP 抗体反应，表明存在 GIP 的截断形式。该细胞群体代表了小鼠中总 GIP 免疫反应性细胞的约 5-15%，具体取决于肠的区域，并且在缺乏 PC2 的小鼠中几乎不存在。酰胺化的 GIP(1-30)和 GIP(1-42)在刺激灌流小鼠胃中的生长抑素释放方面具有相当的效力。因此，GIP(1-30)代表一种天然存在的、具有生物活性的 GIP 形式。
