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.