Active immunization against (Pro(3))GIP improves metabolic status in high-fat-fed mice.
OBJECTIVE
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.


CONCLUSIONS
These results suggest that immunoneutralization of GIP represents an effective means of countering the disruption of metabolic processes induced by high-fat feeding.
Montgomery
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IA
SAAD Centre for Pharmacy and Diabetes, School of Biomedical Sciences Research Institute, University of Ulster, Coleraine, UK.
Irwin
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N
Flatt
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PR
D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology*; D001786:Blood Glucose / Q000378:metabolism*; D001835:Body Weight / Q000502:physiology; D004041:Dietary Fats / Q000008:administration & dosage*; D005749:Gastric Inhibitory Polypeptide / Q000008:administration & dosage / Q000097:blood / Q000276:immunology*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology; D008055:Lipids / Q000097:blood; D008297:Male; D051379:Mice; D009765:Obesity / Q000188:drug therapy / Q000517:prevention & control*; D010179:Pancreas / Q000378:metabolism
D057134:Antibodies, Neutralizing; D001786:Blood Glucose; D004041:Dietary Fats; D007328:Insulin; D008055:Lipids; C549100:pro-glucose-dependent insulinotropic polypeptide; D005749:Gastric Inhibitory Polypeptide