The protein encoded by this gene is actually a preproprotein that is cleaved into four distinct mature peptides. One of these, glucagon, is a pancreatic hormone that counteracts the glucose-lowering action of insulin by stimulating glycogenolysis and gluconeogenesis. Glucagon is a ligand for a specific G-protein linked receptor whose signaling pathway controls cell proliferation. Two of the other peptides are secreted from gut endocrine cells and promote nutrient absorption through distinct mechanisms. Finally, the fourth peptide is similar to glicentin, an active enteroglucagon.

The exons 2-6 of mouse Gcg gene that encode the full-length protein were replaced by human GCG exons 2-6 in B-hGCG mice.

Human Glucagon and human GLP1 were detected in serum of homozygous B-hGCG mice

Gene targeting strategy for B-hGCG mice. The exons 2-6 of mouse Gcg gene that encode the full-length protein were replaced by human GCG exons 2-6 in B-hGCG mice.

Strain specific GCG expression analysis in wild-type C57BL/6 mice and homozygous humanized B-hGCG mice by ELISA. Serum was collected from wild-type C57BL/6 mice (+/+) and homozygous B-hGCG mice (H/H) (n=3, 7-week-old). Protein expression level of GLP1 and Glucagon were analyzed by ELISA. Human GLP1 and human Glucagon were exclusively detectable in homozygous B-hGCG mice.