Glucagon

Glucagon was first identified in 1923 by Kimball and Murlin, who discovered a substance in pancreatic extracts that caused hyperglycemia, which they named glucagon . Over the past century, the importance of glucagon in human physiology and disease has been extensively studied, leading to the development of drugs targeting the glucagon receptor family to treat metabolic diseases .

Glucagon is a 29-amino acid polypeptide with a molecular mass of 3485 daltons . Its primary structure in humans is:

NH2 - His - Ser - Gln - Gly - Thr - Phe - Thr - Ser - Asp - Tyr - Ser - Lys - Tyr - Leu - Asp - Ser - Arg - Arg - Ala - Gln - Asp - Phe - Val - Gln - Trp - Leu - Met - Asn - Thr - COOH

The hormone is synthesized and secreted from alpha cells (α-cells) of the islets of Langerhans, located in the endocrine portion of the pancreas . Glucagon is produced from the preproglucagon gene (Gcg). Preproglucagon first has its signal peptide removed by signal peptidase, forming the 160-amino acid protein proglucagon. Proglucagon is then cleaved by proprotein convertase 2 to glucagon in pancreatic islet α cells .

Glucagon’s primary function is to raise blood glucose levels, preventing hypoglycemia . It achieves this by:

• Triggering the liver to convert stored glycogen into glucose (glycogenolysis) and release it into the bloodstream .
• Preventing the liver from taking in and storing glucose, ensuring more glucose stays in the blood .
• Helping the body make glucose from other sources, such as amino acids .

Glucagon works in opposition to insulin, which lowers blood glucose levels. Together, glucagon and insulin form a feedback system that maintains stable blood glucose levels .

Glucagon is also used as a medication to treat various health conditions, particularly in emergency situations for people with Type 1 diabetes experiencing severe hypoglycemia . Synthetic forms of glucagon can be administered as injections or nasal sprays to quickly raise blood sugar levels .

Recent studies have shown that glucagon production may also occur outside the pancreas, with the gut being a potential site of extrapancreatic glucagon synthesis . This discovery opens new avenues for understanding glucagon’s role in human physiology and its potential therapeutic applications.