Glucagon Receptor

Glucagon receptors are members of the family of g-protein linked receptors (GPLR) that transduce an extracellular signal into an intracellular signal via ligand binding and G-protein activation. These receptors are found throughout the body, with primary sites being the liver and kidney, and secondary sites including the heart, adipose tissue, spleen, and gastrointestinal tract. Following stimulation of the receptor, the second messenger system via adenylate cyclase and cyclic AMP enhance the signal. The primary hormone agonist is glucagon, while a primary antagonist (which blocks the binding site of the receptor) is acylated aminothiophene nitril. The functions of glucagon and its receptors are as vital to the regulation of blood sugar as is insulin. Therefore, glucagon receptors are inherently important to the obesity and diabetes epidemics in society today.

The primary function of the receptor is to bind with glucagon to form a ligand and to carry out the functions of glucagon via the second messenger system. Glucagon itself is hormone secreted by the alpha cells of the islets of Langerhans in the pancreas. The primary functions of glucagon are to stimulate the breakdown of liver glycogen (glycogenolysis) and to increase gluconeogenesis in the liver to increase blood levels of glucose. Other effects of glucagon include activating adipose cell lipase (which makes fatty acids more available to the body) and inhibiting storage of triglycerides in the liver.

Glucagon's functions are regulated by several factors. If levels of glucagon are increased in the blood and antagonists remain stable; there is a greater chance of glucagon binding to a receptor and thereby imposing it functions. Glucagon levels are increased by increased blood amino acids (i.e., protein ingestion) as well as by exercise. The primary inhibitor of glucagon release is hyperglycemia, or high blood glucose.

While most people are currently concerned about diabetes mellitus in conjunction with insulin levels, tumors causing excess glucagon release from the pancreas can be a major obstacle as well. As described, the excess glucagon will continue to bind to multiple receptors, resulting in excessive hyperglycemia. The excess sugar that is not used will then be stored as fat.

A new drug that has shown potential in the scientific research for treating Type 2 diabetes is known as dual-acting peptide for diabetes (DAPD). It combines the promotion of insulin secretion via a compound [Page 331]known as glucagon-like peptide-1 with the effects of antagonistic action on glucagon receptors. It is currently being developed as a novel dual-acting peptide to treat Type 2 diabetes without gastrointestinal side effects.