KEY PRINCIPLES:

• Insulin and glucagon are regulatory hormones that coordinate the storage and release of nutrients into the body
  • Insulin, the “hormone of excess,” promotes the storage of glucose, fatty acids, and amino acids
  • Glucagon, the “hormone of starvation,” promotes formation of glucose and fatty acids

KEY TERMS

• Glycogenolysis is the process by which glycogen is broken down to form glucose
• Gluconeogenesis is the process by which glucose is formed from non-carbohydrate substances (i.e., not glycogen)
• Glycogenesis is the formation of glycogen from glucose (so, the opposite of glycogenolysis)
• Glycolysis is the breakdown of glucose (which generates ATP, and is addressed in detail, elsewhere)

INSULIN

Actions

Insulin lowers blood glucose, amino acid, fatty acid, and potassium concentrations.

• Moves these substances out of the blood and into the cells.
• Promotes their storage and prohibits further synthesis.
  • Glucose is stored as triglycerides and glycogen within adipose (fat) and skeletal muscle tissue.
  • Within the liver, insulin prohibits glyconeogensis (glucose formation), and promotes glycolysis (glucose breakdown).
  • Insulin increases the storage of fatty acids in adipose tissue, and inhibits lipolysis.
  • Insulin promotes amino acid and protein uptake by skeletal muscle tissue and increases protein synthesis; it inhibits protein degradation.
  • Insulin increases sodium-potassium pump activity, which increases cellular potassium uptake.

Clinical Correlation:

A consequence of insulin insufficiency (Type I diabetes) is hyperkalemia, because potassium shifts to the extracellular fluid. Hyperkalemia presents with weakness, chest pain, and difficulty breathing.

Insulin Release

• Stimulation of pancreatic beta cells release insulin, which then enters the hepatic portal system; recall that the hepatic portal system carries venous blood from the digestive organs.
• From the hepatic portal system, insulin is carried to the heart and enters the systemic circulation to be delivered to its target tissues, which, as we indicated above, primarily include the liver, adipose, and skeletal muscle tissue.

Stimuli for Release

In general, insulin is released after a meal.

• Increased blood glucose (most important), fatty acid, and amino acid concentrations
• Increased gastric secretion, particularly of incretins(i.e., GIP and GLP-1)
• Vagal stimulation

Inhibition of Release

• Low blood glucose concentration
• Increased fasting and/or exercise
• Catecholamines (norepinehrine and epinephrine),
• Somatostatin; recall that somatostatin is released from the delta cells of the pancreas.

GLUCAGON

Actions

• Raises blood glucose and fatty acid concentrations via stimulation of glucose and fatty acid mobilization in the liver.
• Promotes gluconeogenesis, glyconeogenesis, and glycogenolysis, which leads to increases in blood glucose concentrations.
• Increases lipolysis and decreases triglyceride storage, so that fatty acids are released into the blood stream.

Glucagon Release

• Pancreatic alpha cells release glucagon, which, like insulin, enters the hepatic portal system;
• Primary target tissue is the liver itself, which we saw in our previous diagram.
• Released between meals or upon ingestion of proteins.

Stimuli for Release

• Low blood glucose concentrations,
• Increased blood protein levels, and
• Increased gastric secretions, particularly of CCK (which, as you may recall, is itself released in response to protein ingestion).
• Catecholamines; this makes sense as part of the “fight or flight” response, a time when our tissues, particularly skeletal tissues, would need all available sources of fuel.

Inhibition of Release

• High levels of blood glucose and fatty acid concentrations
• Elevated levels of insulin
• Somatostatin
  • Somatostatin inhibits both insulin and glucagon release; thus, these three pancreatic endocrine secretions co-ordinate to maintain homeostatic blood nutrient concentrations.