Production of a rat pancreatic polypeptide-specific monoclonal antibody and its influence on glucose homeostasis by in vivo immunoneutralization.
To test the effect of endogenous pancreatic polypeptide (PP) on rat hepatic glucose homeostasis by immunoneutralization, a rat PP-specific monoclonal antibody (MAb) was produced. Binding of this IgG1 monoclonal antibody was inhibited 50% by 350 pM rat PP. Immunohistochemistry showed that the antibody produced the expected pattern of endocrine cell staining in rat pancreas. Groups of six adult male Sprague-Dawley rats were given 5 mg of Protein-A-purified anti-PP MAb or anti-KLH MAb (control) ip every 48 hr for 5 dosing intervals. The rate of hepatic glucose output during isolated liver perfusion was 0.25 +/- 0.03 mg/g/min for the PP MAb-treated rats and 0.17 +/- 0.02 mg/g/min for the control group (p < 0.05). Liver glycogen content was 21.8 +/- 2.9 mg/g for the PP MAb-treated rats and 14.7 +/- 2.4 mg/g for the control group (N = 5). Chronic in vivo immunoneutralization of PP with this new monoclonal antibody suggests that PP influences glucose homeostasis in the rat by affecting hepatic glucose output.
VA/UCLA Gastroenteric Biology Center/Department of Medicine, University of California, Los Angeles 90024, USA.
H C
HC
Wong
D K
DK
Andersen
C
C
Sternini
C L
CL
Ruiz
E C
EC
Hull
J H
JH
Walsh
F C
FC
Brunicardi
D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis* / Q000494:pharmacology / Q000502:physiology*; D000918:Antibody Specificity / Q000502:physiology; D002459:Cell Fusion / Q000276:immunology; D005947:Glucose / Q000276:immunology / Q000502:physiology*; D006706:Homeostasis / Q000276:immunology*; D006825:Hybridomas; D008099:Liver / Q000276:immunology / Q000502:physiology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010191:Pancreatic Polypeptide / Q000276:immunology* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000911:Antibodies, Monoclonal; D010191:Pancreatic Polypeptide; D005947:Glucose