Pancreas Hormones and insulin

The pancreas has two  parts:

1. The endocrine pancreas → releases hormones into the bloodstream, like typical endocrine glands. 

2. The exocrine pancreas → sends digestive juices through a duct outside of an epithelial surface, like into the digestive tract. 

The endocrine part has three main types of hormone secreting cells grouped together into the islets of Langerhans:

1. Alpha cells make glucagon, which raises blood sugar.

2. Beta cells make insulin, which lowers blood sugar.

3. Delta cells make somatostatin, which slows down the release of both insulin and glucagon.

Which hormone lowers blood sugar effectively?

Insulin, its the only hormone that effectively lowers blood sugar

glucagon

the opposite of insulin, it raises blood sugar

somatostatin

 reduces the release of both insulin and glucagon. 

What triggers the release of insulin?

A rise in blood glucose after a meal triggers insulin release.

how insulin acts on target cells

1. Blood glucose rises (usually after a meal).

2. Pancreas releases insulin into the bloodstream.

3. Insulin travels to target tissues (muscle, liver, fat).

4. Insulin binds to its receptor on the target cell’s surface.

   • The receptor has 2 alpha subunits outside the cell and 2 beta subunits spanning the membrane.

5. Binding activates the receptor, triggering changes inside the cell via the beta subunits.

6. Intracellular signaling cascades begin inside the cell.

7. Glucose transporter proteins (like GLUT4) are moved to the cell membrane (especially in muscle and fat).

8. Glucose is taken up from the blood into the cell through these transporters using faciliatted diffusion (no ATP)

9. Glucose is stored or used for energy within the cell.

How does insulin use its affects

Insulin works by attaching to special receptors on the surface of target cells.These receptors are made of 4 parts:

1. 2 alpha subunits sit outside the cell

2. 2 beta subunits pass through the cell membrane and stick into the inside of the cell (cytoplasm)

How does insulin bind to receptors on target cells?

Insulin attaches to the alpha subunits of the receptor. This triggers autophosphorylation of the beta subunits (they add phosphate groups to themselves), turning them into protein kinases. These kinases activate production of proteins that are inserted into the cell membrane as glucose transporters, allowing glucose to enter the cell by facilitated diffusion.

Between meals and insulin

At rest and between meals, muscles take in little glucose because insulin levels are low, so muscles mainly use fatty acids for energy. After a big meal, insulin rises and muscles absorb more glucose, especially if exercising, preferring glucose over fatty acids.

Why do muscles prefer glucose over fatty acids after a meal with insulin present?

Insulin blocks the release of fatty acids from fat tissue, so muscles use glucose for energy instead of fatty acids during times of high insulin, such as after eating and exercising.

What happens to extra glucose in muscles after a meal when not exercising?

Muscles store extra glucose as glycogen in muscle and liver cells to use later for energy.

How do muscles use glycogen during intense exercise?

Muscles break down glycogen into lactic acid to produce energy anaerobically (without oxygen) during short, intense exercise bursts.

How does the liver use glycogen between meals?

When blood sugar drops, the liver converts glycogen back into glucose and releases it into the bloodstream to maintain stable blood sugar levels.

Does inuslin stop the liver from breaking down stored glyocgen?

Yes, Insulin blocks an enzyme called glycogen phosphorylase, which normally breaks glycogen into glucose. This keeps glycogen stored in the liver. Insulin increases the activity of glucokinase, an enzyme that adds a phosphate group to glucose, trapping it inside liver cells for use or storage.

How insulin helps store glucose in the liver

Insulin activates enzymes like phosphofructokinase (helps break down glucose for energy) and glycogen synthase (joins glucose molecules together) so glucose is stored as glycogen.

What happens to insulin levels when blood glucose drops between meals?

The pancreas releases less insulin, while glucagon levels increase.

How does glucose leave the liver to enter the bloodstream?

Glucose phosphatase removes the phosphate from glucose phosphate, allowing free glucose to exit the liver cells and enter the blood.

What happens to extra glucose that cannot be stored as glycogen in the liver?

Insulin helps convert excess glucose into fatty acids, which are packaged into VLDLs and sent to fat tissue to be stored as fat. Insulin also helps fat tissue use glucose to make glycerol, necessary for fat storage.

How do brain cells take in glucose?

Brain cells do not need insulin to take in glucose - they are naturally able to absorb glucose without insulin’s help. Also brain cells can only use glucose as their source of energy.

How does insulin promote fat storage in the body?

Insulin makes most body tissues use glucose for energy instead of fat, encourages the liver to produce fatty acids, and helps fat tissue store fat by blocking fat breakdown enzymes.

• Insulin blocks hormone-sensitive lipase, which normally breaks down stored fat and releases fatty acids into the blood.

How does insulin help glucose contribute to fat storage inside fat cells?

Insulin helps glucose enter fat cells, where most glucose is converted to alpha-glycerophosphate, which provides glycerol to combine with fatty acids forming triglycerides (the main fat storage form).

Why can blood appear milky in someone with diabetes?

Without enough insulin, fat cells can’t absorb fatty acids from the liver, so fatty acids accumulate in the blood, making it look milky.

What happens to fat metabolism between meals when insulin levels are low?

Hormone-sensitive lipase is activated, breaking down triglycerides in fat tissue, releasing fatty acids into the blood to be used as the main energy source.

How can excess fatty acids in the blood affect health in severe diabetes?

The liver converts excess fatty acids into phospholipids, cholesterol, and triglycerides, releasing them as lipoproteins that can build up and cause atherosclerosis.

Insulin deficiency

leads the liver to produce too much acetoacetic acid and reduces the ability of other tissues to use it. Because acetoacetic acid isn't being used properly, the body makes  ß-hydroxybutyric acid and acetone—called ketone bodies—which cause a condition called ketosis.

• usually acetoacetic acid is used as an alternative energy source when glucose is low

• Animals with ketosis often have a sweet smell on their breath. 

Effects of Insulin Deficiency on Glucose

When insulin is deficient, glucose cannot enter most body cells efficiently, causing blood glucose levels to rise (hyperglycemia). Cells become starved for glucose and start using fat and protein for energy. The liver produces more glucose by breaking down glycogen and through gluconeogenesis, worsening hyperglycemia. Excess glucose is lost in urine, leading to dehydration and diabetes symptoms.

Amino acid transport (Insulin)

Insulin helps move amino acids into cells for protein synthesis.

• Insulin activates ribosomes to make proteins by translating mRNA; this step doesn't happen without insulin.

• Prolonged insulin exposure increases transcription and production of enzymes for storing nutrients.

How does insulin affect gluconeogenesis in the liver?

Insulin reduces gluconeogenesis by lowering the activity of enzymes that make glucose from amino acids, preserving amino acids for protein synthesis.

What happens to protein metabolism when insulin is lacking?

Protein storage stops, proteins are broken down, and amino acids enter the blood to be used for energy or gluconeogenesis

How does protein loss affect the body when insulin is deficient?

The body excretes more urea, leading to muscle weakness and impaired organ function due to protein loss.

Insulin + growth hormone

Both hormones are required for normal growth; they work together by performing distinct roles.

Control of insulin secretion

• Insulin secretion is mainly controlled by blood glucose levels, but other factors also influence it like:

1. Blood amino acids

2. Gastrointestinal hormones

3. Glucagon 

4. Growth hormone

5. Cortisol 

6. And to a lesser extent progesterone, estrogen, and nerve signals from parasympathetic and sympathetic nervous systems. 

• After eating, insulin levels in the blood rise quickly, about 10 times higher than normal within 3-5 minutes. 

• Then the level drops about 5 times normal within 5-10 minutes. 

• Around 15 minutes after the meal, insulin levels rise again and eventually reach a steady level that is about 5 times higher than normal after 2 or more hours. 

• This pattern shows how blood glucose levels provide quick feedback to the pancreas to control insulin release. 

What condition must be met for amino acids to strongly stimulate insulin release?

Amino acids like arginine and lysine must rise in the blood along with glucose to strongly stimulate insulin; this combined effect doubles insulin release compared to glucose alone.

Role of Gastrointestinal Hormones in Insulin Secretion

Gastrointestinal hormones are released before glucose from food is absorbed and cause a small initial insulin release. When blood glucose rises afterward, these hormones double insulin secretion.

How do hormones like glucagon, growth hormone, and cortisol affect insulin over time?

When present in large amounts for a long time (or used medically/steroid use), these hormones can overwork the islets of Langerhans and lead to diabetes mellitus.

What medical conditions are often associated with hormone-related diabetes?

Diabetes can occur in people with growth hormone-secreting tumors (e.g., gigantism or acromegaly) or those with excess glucocorticoid production from adrenal glands or tumors.

Type 1 diabetes mellitus

Type 1 diabetes is an autoimmune disease that reduces insulin secretion from pancreatic beta cells. It can be triggered by inherited genetic risk, viral infections, or overactivity of other hormones. If one identical twin has Type 1 diabetes, the other has a ~65% chance of developing it.

• symptoms:

1. hardening of arteries (atherosclerosis)

2. Higher risk of infections

3. High blood pressure (hypertension)

4. Damage to the retina (diabetic retinopathy)

5. Clouding of the eye lens (cataracts)

6. Long term kidney disease

• These problems are more closely linked to the amount of fat in the blood than to blood sugar levels, therefore managing a diabetic patient’s fat intake is just as important as managing their carbohydrate intake.

Glucose in Urine and Its Effects

When blood glucose levels exceed the kidney's ability to reabsorb glucose, it spills into the urine, pulling water with it due to osmosis. This causes excessive urination (polyuria), dehydration, increased thirst (polydipsia), and can lead to circulatory shock.

Why do people with Type 1 diabetes lose weight even if they eat more (polyphagia)?

Because their cells can't use glucose properly, the body breaks down fat and protein for energy, leading to weight loss and weakness despite increased food intake.

Diabetic Ketoacidosis (DKA)

In insulin deficiency, the body burns fat for energy, producing acidic ketones (e.g., β-hydroxybutyric acid). This lowers blood pH (acidosis), triggers hyperventilation, depletes plasma bicarbonate, and may lead to coma or death if not corrected.

Type 2 diabetes

A condition where insulin is present but cells fail to respond properly due to fewer receptors or impaired internal signaling.

How does overeating contribute to insulin resistance?

Overeating causes frequent insulin release, which eventually lowers insulin receptor numbers, reducing insulin sensitivity.

Can insulin resistance be reversed?

Yes—eating less can restore insulin sensitivity, and exercise increases insulin receptors even without weight loss.

• Exercise increases the number of insulin receptors on cells, helping the body respond better to insulin.

Comparison of type 1 and type 2 diabetes

Hyperinsulinism

A condition caused by excess insulin, either from a pancreatic tumor or external insulin overdose.

• This causes blood glucose levels to drop too low, leading to a condition called “insulin shock”

Insulin shock

A medical emergency caused by dangerously low blood glucose due to too much insulin.

• symptoms incliude anxuety, sweating, shaking, hallucinations, seizures and coma if untreated

Diabetic coma vs. insulin shock

Diabetic coma shows fruity breath and deep breathing; insulin shock lacks these symptoms.