Targeting LEAP2 to treat type 2 Diabetes
Staff: Astrid Hauge-Evans, Michael Patterson
Diabetes is one of the most well-known and rapidly expanding chronic metabolic conditions, affecting more than 4.8 million people in the UK today. Both obesity and increased blood sugar are important factors in the development of type 2 diabetes (T2D). They are controlled by hormones such as insulin and ghrelin. Ghrelin stimulates food intake, promotes weight gain and inhibits insulin secretion from islets in the pancreas, which in turn leads to higher blood sugar levels. Our previous work with pancreatic islets has shown that ghrelin also influences the survival of pancreatic islets; a key factor in T2D. Interestingly, we observed sex specific differences, which may suggest potential diabetic medicines based on ghrelin may work differently in men and women. Our current project, funded by the Diabetes Research and Wellness Foundation, focuses on Liver-Enriched Antimicrobial Peptide-2 (LEAP2), an endogenous protein that blocks ghrelin. We have found that LEAP2 modulates insulin secretion from pancreatic islets and thus may be a useful target for T2D medicines, but as with ghrelin this may depend on sex specific differences which need to be understood. Parallel to our work on pancreatic islets, our PhD student Halimah Rustrum, who is funded by the Kuwait Government (Kuwait Cultural Office), is examining blood LEAP2 levels and their relationship to glucose and insulin in healthy individuals compared to those with obesity and T2D. Together, we hope this research will help establish whether LEAP2 can be targeted to treat T2D.