A) Mechanisms Underlying the Production and Function of the Incretin Hormone GLP-1. The proglucagon gene (Gcg) encodes three major peptide hormones, namely glucagon (produced in pancreas), glucagon-like peptide-1 (GLP-1) and GLP-2 (both are produced mainly in intestines). These hormones exert opposite or overlapping functions in controlling blood homeostasis, food intake, cell growth and proliferation. Based on the features of GLP-1, two new categories of drugs, namely GLP-1 analogues and DPP-IV inhibitors, have been developed for T2D treatment. We are exploring mechanisms underlying the production and function of peptide hormones encoded by Gcg, including GLP-1. We are now studying the role of Wnt signalling and the crosstalk between Wnt and other signalling pathways in regulating the expression and function of GLP-1.

B) Mechanisms Underlying the Expression and Function of the Lipogenic Gene Carbohydrates Response Element Binding Protein (ChREBP). The transcription factor ChREBP is a “master controller” of lipogenic genes that encode a battery of enzymes for converting carbohydrates into lipids. The function of ChREBP can be turned on by hyperglycemia and its expression was shown to be increased in obesity and hyperinsulinemia animal models. We are studying molecular mechanisms underlying the expression of ChREBP and its targets.