Question

When GLP-1 is released to the plasma, what are the target cells? What receptor does it bind to? Which intracellular signalling pathway is activated?

Answer 1

Glucagon like peptide 1 regulates the levels of plasma glucose. GLP-1 signals via its receptor to increases the secretion of insulin from the beta cells of the islets of Langerhans in the pancreas. GLP-1 binds to the GLP-1R receptor, a class B-G protein coupled receptor. This leads to a conformational change in the receptor. The GDP on the G alpha of the G protein is replaced by GTP via the guanine exchange factor. The GTP-Galpha is hydrolyzed and will activate adenylyl cyclase. The adenylyl cyclase will break down ATP to cAMP. Protein kinase A is activated by cAMP. The activation of PKA, leads to increase in intracellular calcium, which then closes the K-ATP channels to induce insulin secretion from beta cells of the pancreas.

GLP-1 receptors are also found in adipocytes, liver, gastric mucosa, heart and lung cells. It will increase the synthesis of glycogen in liver along with increased glycolysis and glucose oxidation.