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

Diabetes, Obesity & Metabolism
I A MontgomeryP R Flatt

Abstract

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. 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. 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 indepen...Continue Reading

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Citations

Jul 8, 2015·Molecular and Cellular Endocrinology·Brian FinanTimo D Müller
Sep 26, 2013·Current Opinion in Pharmacology·Nigel Irwin, Peter R Flatt
Nov 21, 2012·International Journal of Obesity : Journal of the International Association for the Study of Obesity·N IrwinP R Flatt
Aug 9, 2018·Pharmacological Reviews·T D MüllerM H Tschöp
Mar 18, 2013·Journal of Diabetes Investigation·Yutaka Seino, Daisuke Yabe
Oct 22, 2015·American Journal of Physiology. Endocrinology and Metabolism·Michael O BoylanM Michael Wolfe
Dec 28, 2010·Biochemical and Biophysical Research Communications·Barry D KerrVictor A Gault

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