The insulinotropic region of gastric inhibitory polypeptide; fragment analysis suggests the bioactive site lies between residues 19 and 30.
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.
Morrow
G W
GW
Department of Physiology, University of British Columbia, Vancouver, Canada.
Kieffer
T J
TJ
McIntosh
C H
CH
MacGillivray
R T
RT
Brown
J C
JC
St Pierre
S
S
Pederson
R A
RA
D000818:Animals; D005749:Gastric Inhibitory Polypeptide / Q000737:chemistry* / Q000502:physiology*; D005753:Gastric Mucosa / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000502:physiology*; D008297:Male; D010179:Pancreas / Q000187:drug effects; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D013004:Somatostatin / Q000502:physiology*; D013997:Time Factors
D007328:Insulin; D013004:Somatostatin; D005749:Gastric Inhibitory Polypeptide; D005947:Glucose