Differential processing of pro-glucose-dependent insulinotropic polypeptide in gut.
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.
Fujita
Yukihiro
Y
Department of Cellular and Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, Canada.
Asadi
Ali
A
Yang
Gary K
GK
Kwok
Yin Nam
YN
Kieffer
Timothy J
TJ
D000818:Animals; D019858:Enteroendocrine Cells / Q000378:metabolism*; D045683:Furin / Q000096:biosynthesis; D005749:Gastric Inhibitory Polypeptide / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D005753:Gastric Mucosa / Q000378:metabolism; D006801:Humans; D051379:Mice; D010446:Peptide Fragments / Q000378:metabolism* / Q000502:physiology; D045664:Proprotein Convertase 1 / Q000378:metabolism*; D045706:Proprotein Convertase 2 / Q000378:metabolism; D013004:Somatostatin / Q000378:metabolism; D013270:Stomach / Q000187:drug effects
D010446:Peptide Fragments; C549099:gastric inhibitory polypeptide (1-30); C549100:pro-glucose-dependent insulinotropic polypeptide; D013004:Somatostatin; D005749:Gastric Inhibitory Polypeptide; D045683:Furin; D045664:Proprotein Convertase 1; D045706:Proprotein Convertase 2