Immunometabolic roles and therapeutic potential of glucose-dependent insulinotropic polypeptide (GIP)

Obesity, type 2 diabetes, and cardiovascular disease share common features, including inflammation in multiple tissues. Inflammation arising in the context of diabetes or obesity is thought to contribute to some of the complications of these disorders, including increased risk of cancer and, most notably, higher rates of heart attacks and strokes. Inflammation may arise in part from the gut, which harbours bacterial organisms and products. Inflammation in turn induces the secretion of some gut peptides — hormonal messengers that relay signals from the gut to distant tissues, including immune cells.

Preliminary data suggest that the increased action of a gut hormone known as glucose-dependent insulinotropic polypeptide (GIP) suppresses inflammation, whereas reduced or complete absence of GIP has the contrary effect, with adverse consequences for metabolism and accelerated development of atherosclerosis. There are currently multiple drug development programs under way to explore whether modulation of GIP activity might be a useful therapeutic approach to treat metabolic disorders such as diabetes and obesity. This project aims to understand how GIP controls inflammation in adipose tissue immune cells and in blood vessels susceptible to the development of atherosclerosis.

This project was selected for funding through the fifth research competition of the Joint Canada-Israel Health Research Program. This initiative is a partnership between IDRC, the Canadian Institutes of Health Research, the Israel Science Foundation, and the Azrieli Foundation.