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Insulin, Glucagon, & Glucose Homeostasis

Insulin, Glucagon, & Glucose Homeostasis

Here we'll learn about insulin and glucagon, and how together, they maintain stable blood glucose levels.

Plasma glucose levels are typically kept at approximately 90 mg/dL of plasma, though this raises and lowers after a meal and in times of fasting.

Homeostatic levels are important to maintain because too much glucose (hyperglycemia) can lead to dehydration, hypotension, and vascular collapse, but too little glucose (hypoglycemia) starves the brain and other tissues of fuel.

Review Diabetes Mellitius Pathophysiology

Co-ordination

Insulin and glucagon are regulatory hormones – that is, they co-ordinate the storage and release of nutrients into the body, based upon its needs.

Insulin is sometimes called the "hormone of excess" because it promotes the storage of glucose, fatty acids, and amino acids when their levels in the blood are high ("excess").

Glucagon is the "hormone of fasting" because it promotes the mobilization of glucose and fatty acids when their blood levels are low (in periods of fasting).

"Mobilization" means that glucagon promotes the breakdown and release of stored nutrients for use by the body tissues.

Key processes

Maintain blood glucose levels within a narrow range:

The first two processes are stimulated by insulin and remove glucose from the bloodstream:

Glycogenesis is the formation of glycogen from glucose. Glycogen comprises connected glucose molecules; it is the primary storage form of glucose in humans.

Glycolysis is the breakdown of glucose to generate ATP.

The next two processes raise blood glucose levels and therefore increase its availability for use in the body tissues:

Glycogenolysis is the process of breaking down glycogen to form glucose ("glycogen" + "olysis" is glycogen breakdown).

Gluconeogenesis is the creation of glucose from non-carbohydrate substances (gluco = glucose, neo = new, genesis = creation). In other words, this is an alternative way for the body to make glucose available, without breaking down glycogen.

Insulin & Glucagon Effects

Next, let's learn more about the effects of insulin and glucagon in their target tissues.

Insulin primarily acts on striated muscle, the liver, and adipose; glucagon primarily acts on the liver.

Note that this is a simplification; for example, glucagon can have metabolic effects in the muscle and adipose tissue, but this is typically only seen at very high levels.

INSULIN

Insulin is released from pancreatic beta cells after a meal; its overall effects are to promote nutrient storage.

Specifically, show that:

In the striated muscle, insulin promotes glycogenesis, glycolysis, and protein synthesis; insulin inhibits proteolysis.

Simply put, insulin promotes the uptake and storage of glucose and amino acids to build muscle mass.

In the adipose, or fat, tissue, insulin promotes triglyceride formation from fatty acids and fat storage; it inhibits lipolysis.

Again, we see that insulin's overall effects are to promote nutrient storage.

In the liver, insulin promotes glycogenesis, which stores glucose as glycogen. Insulin also promotes glycolysis, which removes glucose from the blood. Insulin inhibits glycogenolysis to prevent glycogen breakdown, and, it inhibits ketogenesis, which is the breakdown of fatty acids to form ketone bodies.

Though not included in our diagram, be aware that insulin also increases sodium-potassium pump activity and, therefore cellular uptake of potassium; thus, insulin insufficiency is associated with hyperkalemia (elevated blood potassium).

Next, indicate that glucagon is released from pancreatic alpha cells during periods of fasting; overall, its effects are to promote nutrient mobilization.

GLUCAGON

In the liver: Glucagon promotes glucose synthesis via glycogenolysis and gluconeogenesis, which elevates blood glucose levels and fuel availability for the tissues.

Glucagon also stimulates ketogenesis in the liver; the resulting ketone bodies are used as an alternative form of energy when glucose is not readily available for fuel.

Let's summarize the actions of insulin and glucagon in a table.

We can think of these hormones as promoting either nutrient storage or nutrient mobilization:

The following processes facilitate nutrient storage:

Glycogenesis (storage of glucose as glycogen)
Lipogenesis (storage of fatty acids as triglycerides)
Protein synthesis (storage of amino acids)

Insulin increases these processes and glucagon decreases them.

Note that insulin also promotes glycolysis, which removes glucose from the blood.

The following processes that facilitate nutrient mobilization:

Glycogenolysis & Gluconeogenesis (which produce glucose for fuel)
Lipolysis (which provides fatty acids for fuel)
Ketogenesis (which provides ketone bodies for fuel).

Insulin decreases these processes and glucagon increases them.

Note that some of these effects are only seen when insulin or glucagon are present at high levels; for example, the lipolytic effects of glucagon are likely unimportant under normal physiologic conditions.

Insulin & Glucagon Regulation

Lastly, let's learn what stimuli and inhibitors regulate insulin and glucagon secretion.

Insulin:

Insulin is secreted in response to: High levels of glucose, amino acids, and fatty acids (all of which rise after a meal), acetylcholine, incretins, and glucagon.

Insulin secretion is inhibited by catecholamines (epinephrine and norepinephrine) and somatostatin.

Glucagon:

Glucagon is secreted in response to: Reduced levels of glucose, elevated levels of amino acids, catecholamines, and acetylcholine.

Glucagon secretion is inhibited by insulin, high glucose levels, and somatostatin.

Pause to notice a few relationships that highlight the complexity of glucose regulation by these two hormones:

As we might expect, high glucose levels stimulate insulin release but inhibit glucagon release.
However, amino acids and acetylcholine stimulate insulin and glucagon release.
Catecholamines inhibit insulin secretion but promote glucagon secretion; this prevents hypoglycemia when nutrient metabolism is elevated, such as during exercise.
The hormones themselves influence each other: Glucagon stimulates insulin secretion, but insulin has the opposite effect and inhibits glucagon secretion.
Somatostatin inhibits both insulin and glucagon; recall that somatostatin is another hormone released by the pancreas.

Diabetes Mellitus

Diabetes mellitus is a condition in which peripheral cells do not respond to insulin; as a result, glucose stays in the blood, leading to hyperglycemia with detrimental effects.

See Full Tutorial on Diabetes mellitus pathophysiology

See Full Tutorial on Diabetes Mellitus Biochemistry

Insulin, Glucagon, & Glucose Homeostasis

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