How is Glucagon Activated?

Glucagon activation is primarily triggered by low blood sugar levels (hypoglycemia). This process involves multiple pathways working in concert.

Several factors stimulate the release of glucagon from the alpha cells of the pancreas:

Low Blood Glucose: This is the most potent trigger. When blood sugar drops, the pancreas responds by releasing glucagon to raise it. [Source: Glucagon Physiology - Endotext - NCBI Bookshelf]
Prolonged Fasting: Extended periods without food lead to low blood glucose, thus activating glucagon release. [Source: Glucagon is secreted in response to hypoglycemia, prolonged fasting, exercise and protein-rich meals (10).]
Exercise: Physical activity can temporarily lower blood glucose, prompting glucagon secretion. [Source: Glucagon is secreted in response to hypoglycemia, prolonged fasting, exercise and protein-rich meals (10).]
Protein-Rich Meals: The ingestion of protein-rich meals also stimulates glucagon release. [Source: Glucagon is secreted in response to hypoglycemia, prolonged fasting, exercise and protein-rich meals (10).]

Regulatory Pathways

Glucagon release isn't solely dependent on blood glucose. It's a complex process influenced by:

Endocrine and Paracrine Pathways: Hormones and local signaling molecules within the pancreas interact to regulate glucagon secretion. [Source: Glucagon release is regulated through endocrine and paracrine pathways; by nutritional substances; and by the autonomic nervous system (11).]
Autonomic Nervous System: The sympathetic nervous system, activated during stress or exercise, increases glucagon release. [Source: Activation of the autonomic nerves, which innervate the islet, increases glucagon secretion.]
Nutritional Substances: The presence of certain nutrients, beyond just glucose, plays a role in modulating glucagon release. [Source: Glucagon release is regulated through endocrine and paracrine pathways; by nutritional substances; and by the autonomic nervous system (11).]

Once released, glucagon acts primarily on the liver to:

Stimulate Glycogenolysis: Break down glycogen (stored glucose) into glucose, releasing it into the bloodstream. [Source: Glucagon causes the liver to engage in glycogenolysis: converting...]
Stimulate Gluconeogenesis: Produce glucose from non-carbohydrate sources like amino acids and glycerol. [Source: Glucagon stimulates gluconeogenesis by INSP3R1-mediated...]
Increase Blood Glucose Levels: The net effect of these processes is an increase in blood glucose levels, countering hypoglycemia. [Source: Glucagon increases your blood sugar level and prevents it...]