Glucagon is a hormone that’s involved in raising the blood glucose levels or glycemia while fasting. Glucagon is produced by some small islands of cells in the pancreas called the Langerhans islets.
The pancreas lies in the upper left part of the abdomen, right behind the stomach.
The vast majority of the pancreas is made up of exocrine glands in charge of secreting digestive enzymes into the small intestine to help digestion.
But about 1 to 2% of the mass of the pancreas is made up of the islets of Langerhans, which are endocrine glands made up by five different cell types, each of which secretes a specific hormone.
The most abundant are the beta cells, which produce insulin.
But you can also find alpha cells that secrete glucagon, delta cells that secrete somatostatin, gamma cells that secrete pancreatic polypeptide, and finally epsilon cells that secrete ghrelin
Let’s focus on alpha cells.
Alpha cells are in charge of producing glucagon, which is a peptide hormone encoded by the GCG gene on chromosome 2.
Glucagon is first synthesized as a single polypeptide called preproglucagon.
Preproglucagon has a short tail called a leader or signal peptide which is cleaved off to form proglucagon, and proglucagon is then further cleaved to form glucagon.
This mature glucagon is stored inside granules within the alpha cells where it waits until it’s released into the blood.
The most important glucagon regulator is glucose.
Apha cells are sensitive to glucose concentrations in blood, and when blood glucose levels are low - for instance during fasting or after intense physical activity - alpha cells secrete glucagon into the blood to help increase those levels.
Glucagon secretion is also stimulated by adrenaline from the sympathetic nervous system, which is activated during stressful situations with high energy consumption.
Glucagon secretion is also stimulated by cholecystokinin which is secreted by intestinal cells to stimulate digestion and absorption.
But when blood glucose is high, alpha cells stop secreting glucagon, and beta cells start secreting insulin, which both lowers glucose levels and inhibits glucagon secretion in the process.