Background: Glucose-dependent insulinotropic polypeptide (GIP) is a gastrointestinal hormone that is secreted in response to food intake and modulates β-cell function. Remarkably, GIP looses its insulinomimetic effect in the presence of chronic hyperglycaemia and thus appears to be ineffective in poorly controlled T2DM at least with regard to insulin release. The mechanism by which this occurs is not clear and it is not known.
Objectives: To analyse the effect of GIP-Infusions on changes in adipose tissue gene expression at different blood-glucose levels in obese men and also detect different biomarkers and hormone interactions caused by GIP.
Setting and participants: Seventeen healthy overweight men (BMI: 2840 kg/m2; age: 30-65 years) underwent a single-blind intervention with euglycaemic or hyperglycaemic clamps in combination with GIP or saline infusions. Each solution was applied at physiological concentrations for four hours. Before and after the infusions biopsies from subcutaneous adipose tissue were taken. We isolated total RNA from all fat biopsies and hybridized the RNA to Agilent Whole Human Genome Microarrays (total 100 arrays). The results were verified by RT-PCR and amended by cell culture experiments.
Results: We identified several genes being involved in inflammatory and proliferative cell signalling. Under euglycaemic hyperinsulinaemic clamp conditions in combinations with a GIP-Infusion we find a significant upregulation of chemokine ligand 2 (CCL-2/MCP-1), interleukin Iβ (IL-1β), fibroblast growth factor receptor 1 (FGFR-1) and oncostatin M (OSM). We also see an activation of cell proliferation by wnt signalling in adipose tissue after exposure with GIP mediated by cyclin D1, frizzeled homolog 4, frizzeled homolog 10 (FZD 4/10) and several zinc finger proteins like ZNF 397, and ZNF 658.
Conclusion: GIP may play a role in cell proliferation and inflammation in adipose tissue of obese men. Dependent from blood glucose levels GIP also effects lipid and glucose metabolism in adipose tissue.
03 - 07 May 2008
European Society of Endocrinology