Active immunisation against gastric inhibitory polypeptide (GIP) improves blood glucose control in an animal model of obesity-diabetes

Nigel Irwin*, Paula L. McClean, Steven Patterson, Kerry Hunter, Peter R. Flatt

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

33 Citations (Scopus)

Abstract

Recent research suggests that long-term ablation of gastric inhibitory polypeptide (GIP) receptor signalling can reverse or prevent many of the metabolic abnormalities associated with dietary and genetically induced obesity-diabetes. The present study was designed to assess the sub-chronic effects of passive or active immunisation against GIP in ob/ob mice. Initial acute administration of GIP antibody together with oral glucose in ob/ob mice significantly increased the glycaemic excursion compared to controls (p<0.05). This was associated with a significant reduction (p<0.05) in the overall glucose-mediated insulin response. However, sub-chronic passive GIP immunisation was not associated with any changes in body weight, food intake or metabolic control. In contrast, active immunisation against GIP for 56 days in young ob/ob mice resulted in significantly (p<0.05) reduced circulating plasma glucose concentrations on day 56 compared to controls. There was a tendency for decreased circulating insulin in GIP immunised mice. The glycaemic response to intraperitoneal glucose was correspondingly improved (p<0.05) in mice immunised against GIP. Glucose-stimulated insulin levels were not significantly different from controls. Furthermore, insulin sensitivity was similar in mice immunised against GIP and respective controls. Overall, the results reveal that active, as opposed to passive, immunisation against GIP improves blood glucose control ob/ob mice.

Original languageEnglish
Pages (from-to)75-80
Number of pages6
JournalBiological Chemistry
Volume390
Issue number1
DOIs
Publication statusPublished - 1 Jan 2009

Keywords

  • active immunisation; gastric inhibitory polypeptide (GIP); GIP antibody; glucose homeostasis; passive immunisation

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Clinical Biochemistry

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