Effects of Insulin and Glucagon Lesson: Definition & Examples

Lesson Overview

• Pancreatic Hormones and Glucose Homeostasis
• Insulin: The Fed-State Hormone
• Metabolic Effects of Insulin (Fed State)
• Glucagon: The Fasting-State Hormone
• Metabolic Effects of Glucagon (Fasting State)
• Regulation and Feedback Control

Insulin and glucagon are two key hormones that maintain the balance of blood glucose (blood sugar) levels. Produced by the pancreas, these hormones have opposite effects: insulin lowers blood glucose by helping cells absorb and store nutrients, while glucagon raises blood glucose by prompting the release of stored fuel. 

Together, insulin and glucagon work in tandem to ensure the body's cells have a steady supply of energy without extreme highs or lows in blood sugar.

Pancreatic Hormones and Glucose Homeostasis

The pancreas contains clusters of hormone-producing cells called the islets of Langerhans, which make up only about 1–2% of the pancreas. These islet cells secrete insulin and glucagon, two hormones with opposite effects that together maintain blood sugar (glucose) balance. Insulin, produced by beta (β) cells, lowers blood glucose by promoting nutrient uptake and storage. Glucagon, from alpha (α) cells, raises blood glucose by stimulating the release of stored fuel. This balance ensures that cells have a steady supply of glucose (the brain depends on glucose because fatty acids cannot cross the blood–brain barrier).

The liver plays a central role in blood glucose regulation and nutrient distribution. In the fed state (high insulin), the liver absorbs glucose and other nutrients from the bloodstream and stores or processes them for use by other tissues. In the fasting state (high glucagon), the liver breaks down its glycogen and produces new glucose to release into the bloodstream. In this way, the liver acts as a "nutrient distribution center," storing energy when it is abundant and providing energy when needed.

Insulin: The Fed-State Hormone

Insulin is a peptide hormone made by pancreatic β-cells and is dominant during the absorptive (fed) state (approximately 2–4 hours after a meal). Its secretion is triggered primarily by a rise in blood glucose (after eating). Elevated blood amino acid levels (after a high-protein meal) also stimulate some insulin release. β-cells detect the high blood sugar (using the enzyme glucokinase as a glucose sensor) and respond by secreting insulin. Insulin is synthesized as a larger precursor (preproinsulin, then proinsulin) that is later processed into active insulin, which is stored in granules until release. The active hormone is secreted directly into the bloodstream.

Mechanism of action: Insulin travels through the circulation and binds to insulin receptors on its target cells (liver, muscle, and adipose tissue). The insulin receptor is a receptor tyrosine kinase. When insulin binds, the receptor's kinase domain becomes activated and phosphorylates itself and various intracellular proteins (including insulin receptor substrate, IRS). This initiates a cascade of signaling events that alter cellular metabolism. A key outcome is that insulin signaling increases the number of glucose transporters (GLUT4) on muscle and fat cell membranes, rapidly boosting glucose uptake from the blood. Insulin's signals also switch on enzymes that build glycogen, fat, and protein, while turning off enzymes involved in breaking down these fuels.

Metabolic Effects of Insulin (Fed State)

In the fed state, insulin has broad anabolic effects – it encourages the body to store excess fuel and build new tissues:

• Liver: Insulin promotes glycogen synthesis in liver cells, storing glucose as glycogen. It also enhances glycolysis (burning glucose for immediate energy). Once glycogen stores are filled, insulin converts excess glucose into fatty acids, which are assembled into triglycerides (fat) for storage (in the liver and in adipose tissue). At the same time, insulin inhibits hepatic gluconeogenesis (new glucose production) and glycogenolysis (glycogen breakdown), preventing the liver from releasing glucose during the fed state.
  
• Muscle: Insulin stimulates glucose uptake into muscle cells (via GLUT4) and promotes glycogen formation in muscle for storage. It also increases amino acid uptake and protein synthesis in muscles while reducing protein breakdown. This allows muscles to grow and store protein when nutrients are plentiful.
  
• Adipose tissue: In fat tissue, insulin greatly increases glucose uptake (providing substrate for fat production) and strongly stimulates fat storage. It activates lipoprotein lipase on fat cell membranes, which releases fatty acids from circulating triglycerides so they can be taken up by adipocytes and made into triglycerides. Meanwhile, insulin inhibits hormone-sensitive lipase, blocking the breakdown of stored fat. Thus, insulin causes adipose tissue to accumulate fat after meals.

By these actions, insulin lowers blood glucose (by moving glucose into cells and storing it) and prevents blood sugar from staying too high after a meal.

Take This Quiz:

Effects of Insulin and Glucagon! Biochemistry Trivia Quiz

Glucagon: The Fasting-State Hormone

Glucagon is a peptide hormone made by pancreatic α-cells and becomes dominant during the post-absorptive (fasting) state (starting a few hours after a meal). Glucagon is released into the bloodstream when blood glucose levels fall (such as between meals or during fasting). A protein-rich meal (high amino acids with low carbohydrate) can also stimulate glucagon release, ensuring that insulin's action doesn't cause hypoglycemia. Additionally, stress hormones like epinephrine (adrenaline) enhance glucagon secretion. When blood glucose is high and insulin is abundant, glucagon release is minimal (insulin helps suppress glucagon release).

Mechanism of action: Glucagon primarily targets the liver. It binds to a receptor on liver cells that activates the cAMP second-messenger system (via a G-protein coupled receptor). The increase in cAMP activates protein kinase A, which phosphorylates key enzymes. This turns on pathways that release glucose and other fuels from the liver. (Skeletal muscle cells lack glucagon receptors, so glucagon's direct actions are largely confined to the liver. Adipose tissue has some response to glucagon, but it is much weaker than the liver's response.)

Metabolic Effects of Glucagon (Fasting State)

In the fasting state, glucagon has catabolic effects – it signals the body to mobilize stored fuels to prevent blood sugar from dropping too low:

• Liver: Glucagon stimulates the liver to break down glycogen (glycogenolysis), releasing glucose into the bloodstream. It also activates gluconeogenesis, causing the liver to make new glucose from other sources (like amino acids and glycerol). Together these processes sharply increase the liver's glucose output, which is critical for maintaining blood glucose (especially to fuel the brain) during fasting. Glucagon also promotes ketone body formation from fatty acids in the liver in prolonged fasting, providing an alternative fuel when glucose is scarce.
  
• Adipose tissue: In fat tissue, low insulin levels (and the presence of glucagon) allow lipolysis to occur. Fat cells break down stored triglycerides into free fatty acids and glycerol, with glucagon helping to activate hormone-sensitive lipase. The fatty acids are released into the blood to be used as fuel by muscles and other tissues, and glycerol travels to the liver to be converted into glucose.
  
• Muscle: Glucagon has no direct effect on muscle (muscle fibers do not have glucagon receptors). In extended fasting, however, low insulin and other hormones cause muscles to break down some proteins, releasing amino acids. These amino acids go to the liver where they are used in gluconeogenesis to help sustain blood glucose.

Take This Quiz:

What do you know about Glucagon? Trivia Quiz

Regulation and Feedback Control

Insulin and glucagon secretion are controlled by negative feedback to stabilize blood glucose. When blood glucose rises above normal (after a meal), β-cells release insulin. Insulin helps cells take in and store glucose, causing blood sugar to drop back toward normal; as it does, insulin secretion slows (feedback inhibition). Conversely, when blood glucose falls below normal (during fasting or exercise), α-cells release glucagon. Glucagon causes the liver to release glucose, raising blood sugar back toward normal; as it rises, glucagon secretion is dialed down. Moreover, insulin and glucagon influence each other: insulin helps restrain glucagon release, so when insulin is low, glucagon secretion increases.

During hypoglycemia (dangerously low blood sugar, below ~55 mg/dL), the body activates additional emergency responses. The adrenal glands secrete epinephrine, which rapidly increases blood glucose by promoting glycogen breakdown and gluconeogenesis in the liver. Epinephrine also triggers the noticeable symptoms of hypoglycemia (causing trembling and sweating) and simultaneously suppresses insulin release while boosting glucagon's effect. These mechanisms collectively prevent severe hypoglycemia and prompt the person to eat. Through the coordinated actions of insulin and glucagon (along with these backup systems), blood glucose is normally kept within a narrow healthy range (around 70–110 mg/dL).

Together, insulin and glucagon keep metabolism in balance. Insulin directs the body to store fuel and use nutrients in the fed state, while glucagon directs the body to release stored fuel and maintain blood glucose in the fasting state. This coordinated system ensures stable blood sugar and energy availability under all conditions.