Pancreatic Hormones: Functions & Mechanism of Action

 

1. Introduction

The pancreas is a vital gland located in the abdomen with both exocrine and endocrine roles. Its endocrine component consists of clusters of cells known as the islets of Langerhans. These islets secrete several hormones that regulate metabolism, digestion, and blood sugar. In this article, we explore the major pancreatic hormones—insulin, glucagon, somatostatin, and pancreatic polypeptide—detailing their functions and mechanisms of action in a clear, natural tone.

Infographic summarizing pancreatic hormones and their cells of origin,
 functions, and signaling mechanisms.

2. Insulin

Source: β-cells of the islets of Langerhans
Main Functions: 

 Lowers blood glucose levels

 Promotes uptake of glucose, amino acids, fatty acids into cells 

 Stimulates glycogen (liver & muscle), fat, and protein synthesis

Mechanism of Action:
Insulin is secreted in response to high blood glucose (e.g., after a meal). It binds to insulin receptors (tyrosine-kinase receptors) on cell surfaces. This triggers a cascade (IRS–PI3K–Akt pathway) that:

1. Mobilizes GLUT4 transporters to the cell membrane → increases glucose uptake.

2. Activates glycogen synthase (via GSK-3 inhibition) → glycogen storage.

3. Enhances fatty-acid synthase and acetyl-CoA carboxylase → fat synthesis.

4. Promotes protein synthesis through mTOR activation. Mechanistic Target of Rapamycin (mTOR) is a central regulator of cell growth, metabolism, and protein synthesis. It is part of a critical intracellular signaling pathway activated by insulin and nutrients like amino acids, especially leucine.

3. Glucagon

Source: α-cells of the islets
Main Functions: 

Raises blood glucose via gluconeogenesis and glycogenolysis 

Promotes lipolysis in adipose tissue

Maintains fasting glucose levels

Mechanism of Action:
Glucagon is released when blood glucose is low (e.g., fasting). It binds GPCRs on hepatocytes, activating Gαs → adenylate cyclase → ↑ cAMP → activates protein kinase A (PKA). PKA:

1. Phosphorylates glycogen phosphorylase → glycogen breakdown.

2. Inhibits glycogen synthase → halts storage.

3. Stimulates gluconeogenic enzymes (PEPCK, G6Pase).

4. Activates hormone-sensitive lipase → fatty-acid release.

4. Somatostatin

Source: δ-cells
Main Functions: 

 Broad inhibitor: reduces release of insulin, glucagon, growth hormone, thyroid-stimulating hormone slows gastrointestinal motility and digestive secretions.

Mechanism of Action:
Somatostatin binds to GPCRs (primarily Gi/o), lowering cAMP in target cells. This downregulates hormone secretion from neighboring pancreatic cells and GI endocrine cells, acting as a paracrine regulator to maintain hormonal balance.

5. Pancreatic Polypeptide (PP)

Source: F-cells (or PP cells)
Main Functions: 

 Inhibits pancreatic exocrine secretion (enzymes, bicarbonate) 

 Regulates gastric emptying 

May influence appetite and hepatic glycogen metabolism

Mechanism of Action:

PP circulates and binds to pancreatic receptor subtypes (likely Y4/Y5), inhibiting secretion and influencing gastrointestinal motility via vagal pathways. Exact signaling cascades are still being researched.

6. Integrated Hormonal Balance

Under normal conditions:

During a meal: ↑ Insulin, ↓ Glucagon → glucose is stored. 

During fasting: ↑ Glucagon, mild insulin → glucose is produced.

Somatostatin and pancreatic polypeptide finetune both phases, preventing overactivity.

Dysfunction in this balance underlies diseases like diabetes mellitus (insulin deficiency/resistance), hypoglycemia, and rare endocrine tumors.

8. Frequently Asked Questions (FAQ)

Q1: What triggers insulin release?
A: Primarily high blood glucose; also presence of amino acids, gastrointestinal hormones (e.g., GIP, GLP‑1), and parasympathetic activation.

Q2: How do insulin and glucagon regulate each other?
A: High glucose → insulin ↑, glucagon ↓. Low glucose → glucagon ↑, insulin ↓. Somatostatin dampens both when secretion is excessive.

Q3: What happens if somatostatin is deficient?
A: Unchecked insulin and glucagon release can cause metabolic imbalance, hypoglycemia, or hyperglycemia, depending on context.

Q4: Is pancreatic polypeptide important clinically?
A: It’s less critical for sugar regulation but plays roles in digestion. Levels may rise in certain pancreatic endocrine disorders.

Q5: Are there clinical drugs mimicking these hormones?
A: Yes—insulin analogs treat diabetes, GLP‑1 agonists (e.g., exenatide) enhance insulin; glucagon injections treat severe hypoglycemia. Somatostatin analogs (e.g., octreotide) are used for endocrine tumors.

References

1. Guyton & Hall, Textbook of Medical Physiology, 14th ed. (Saunders, 2020)

2. Sherwood, Human Physiology: From Cells to Systems, 10th ed. (Cengage, 2021)

3. Boron & Boulpaep, Medical Physiology, 3rd ed. (Elsevier, 2020)