Differential processing of pro-glucose-dependent insulinotropic polypeptide in gut

作者：Fujita Yukihiro; Asadi Ali; Yang Gary K; Kwok Yin Nam; Kieffer Timothy J^*

来源：American Journal of Physiology - Gastrointestinal and Liver Physiology, 2010, 298(5): G608-G614.

DOI：10.1152/ajpgi.00024.2010

• GIP
• incretin
• PCSK
• perfused stomach

Fujita Y, Asadi A, Yang GK, Kwok YN, Kieffer TJ. Differential processing of pro-glucose-dependent insulinotropic polypeptide in gut. Am J Physiol Gastrointest Liver Physiol 298: G608-G614, 2010. First published February 25, 2010; doi: 10.1152/ajpgi.00024.2010. 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 similar to 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.

• 出版日期2010-5