Inkretinsystemets inverkan på hjärt-kärlsjukdom och cancer

The core of this research proposal are the applicant ́s novel findings from two large prospective cohorts showing that elevated levels of glucose-dependent insulinotropic polypeptide (GIP) are causally associated with greater risk of future cardiovascular disease (CVD) and mortality as well as subclinical atherosclerosis,Here the applicant aim to validate how high levels of GIP associates with adverse outcomes also in exclusively diabetic subjects originated from the Swedish All New Diabetics in Scania cohort.

He will furhter explore the mechanisms behind the harmful actions mediated by GIP by taking advantage of two separate heart failure cohorts; for discovery (analysis of myocardial biopsies) and validation (HARVEST.cohort) for the detection of GIP associated proteins that could mediate the GIP-driven risk of CVD and mortality.

The applicant will also, in healthy male subjects investigate the direct effect of GIP infusion on the GIP associated proteins discovered in the two heart failure cohorts. In experimental studies the applicant will examine the long-term (mice) cardiovascular effects of incretin infusion.

To prove upon GIP inhibition as a possible future therapeutic alternative, we will test the potential cardio-protective effects of a validated GIP-receptor antagonist in an experimental myocardial infarction mouse model.

Finally, we invastigate GIP and proglucagon-derived peptide glucagon-like peptide-1 (GLP-1) associations with incident cancer and statin usage.