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Active immunization against (Pro 3 )GIP improves metabolic status in high‐fat‐fed mice
Author(s) -
Montgomery I. A.,
Irwin N.,
Flatt P. R.
Publication year - 2010
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/j.1463-1326.2010.01228.x
Subject(s) - medicine , endocrinology , gastric inhibitory polypeptide , triglyceride , insulin , immunization , obesity , antibody , pancreas , active immunization , cholesterol , chemistry , immunology , glucagon
Aim: Ablation of gastric inhibitory polypeptide (GIP) receptor signalling can prevent many of the metabolic abnormalities associated with dietary‐induced obesity‐diabetes. The present study was designed to assess the ability of active immunization against (Pro 3 )GIP to counter metabolic dysfunction associated with diet‐induced obesity in high‐fat‐fed mice. Methods: Normal male Swiss NIH mice were injected (s.c.) once every 14 days for 98 days with complexed (Pro 3 )GIP peptide, with transfer to a high‐fat diet on day 21. Results: Active immunization against (Pro 3 )GIP resulted in circulating GIP antibody production and significantly (p < 0.05 p < 0.01) reduced circulating blood glucose concentrations compared to high‐fat control mice from day 84 onwards. Glucose levels were not significantly different from lean controls. The glycaemic response to i.p. glucose was correspondingly improved (p < 0.01) in (Pro 3 )GIP‐immunized mice. Furthermore, circulating and glucose‐stimulated plasma insulin levels were significantly (p < 0.01 to p < 0.001) depressed compared to high‐fat control mice. Liver triglyceride, pancreatic insulin and circulating LDL‐cholesterol levels were also significantly reduced in (Pro 3 )GIP‐immunized mice. These changes were independent of any effects on food intake or body weight. The glucose‐lowering effect of native GIP was annulled in (Pro 3 )GIP‐immunized mice consistent with the induction of biologically effective GIP‐specific neutralizing antibodies. Conclusion: These results suggest that immunoneutralization of GIP represents an effective means of countering the disruption of metabolic processes induced by high‐fat feeding.