INSULIN
Introduction
Insulin is a peptide hormone secreted by the β-cells of the
Islets of Langerhans of the pancreas. It is the chief hypoglycemic
hormone of the body and plays a central role in the regulation of glucose
homeostasis.
It promotes:
- Uptake of glucose by cells
- Storage of glucose as glycogen
- Synthesis of fats and proteins
- Growth and anabolic activities
Pancreas as an Endocrine Gland
The pancreas is a mixed gland:
- Exocrine part → secretes digestive enzymes
- Endocrine part → Islets of Langerhans
There are about 1–2 million Islets of Langerhans in humans,
forming approximately 1–2% of pancreatic tissue.
Cells of Islets of Langerhans
|
Cell Type |
Hormone Secreted |
Function |
|
α-cells |
Raises blood glucose |
|
|
β-cells |
Insulin |
Lowers blood glucose |
|
δ-cells |
Somatostatin |
Inhibitory hormone |
|
PP cells |
Pancreatic polypeptide |
GI regulation |
Chemical Nature of Insulin
- Insulin is a protein/peptide
hormone.
- It contains 51 amino acids
- Consists of:
- A-chain → 21 amino acids
- B-chain → 30 amino acids
- Chains are connected by disulfide
bonds
Structure
A-chain (21 aa) ← disulfide bonds →
B-chain (30 aa)
Synthesis of Insulin
Insulin is synthesized in β-cells in several steps.
Steps of Synthesis
1. Formation of Preproinsulin
- Initial inactive precursor
- Synthesized on ribosomes of rough
ER
2. Formation of Proinsulin
- Signal peptide removed
- Proinsulin contains:
- A-chain
- B-chain
- Connecting peptide (C-peptide)
3. Formation of Insulin
- C-peptide removed in Golgi
apparatus
- Mature insulin formed
Preproinsulin → Proinsulin → Insulin +
C-peptide
C-peptide and insulin are released in equal amounts.
C-Peptide
Importance
- Marker of endogenous insulin
secretion
- Helps distinguish:
- Natural insulin production
- Injected insulin use
Clinical Significance
- High C-peptide → body producing
insulin
- Low C-peptide → β-cell failure
Mechanism of Insulin Secretion
Main Stimulus
Increased Blood Glucose
Mechanism
- Glucose enters β-cells via GLUT
transporters
- ATP production increases
- ATP-sensitive K⁺ channels close
- Cell membrane depolarizes
- Ca²⁺ channels open
- Calcium influx occurs
- Insulin released by exocytosis
Flowchart
↑ Blood glucose
↓
Glucose enters β-cell
↓
↑ ATP production
↓
Closure of K+ channels
↓
Depolarization
↓
Opening of Ca2+ channels
↓
Insulin secretion
Factors Affecting Insulin Secretion
Factors Increasing Insulin Secretion
- Increased blood glucose
- Amino acids
- Fatty acids
- Glucagon
- Gastrointestinal hormones
- Parasympathetic stimulation
Factors Decreasing Insulin Secretion
- Fasting
- Sympathetic stimulation
- Somatostatin
- Low blood glucose
Mechanism of Action of Insulin
Insulin acts through a receptor tyrosine kinase present on target
cell membranes.
Steps
- Insulin binds receptor
- Receptor activated
- Phosphorylation cascade initiated
- GLUT-4 transporters move to
membrane
- Glucose uptake increases
Target Organs of Insulin
Main target tissues:
- Liver
- Skeletal muscle
- Adipose tissue
Functions of Insulin
1. Effects On Carbohydrate Metabolism
Insulin lowers blood glucose level.
Actions
In Liver
- Increases glycogenesis
- Decreases glycogenolysis
- Decreases gluconeogenesis
In Muscle
- Increases glucose uptake
- Increases glycogen synthesis
In Adipose Tissue
- Increases glucose utilization
Overall Effect
↓ Blood glucose level
Insulin is therefore called a: “Hypoglycemic Hormone”
2. Effects On Fat Metabolism
Insulin promotes fat storage.
Actions
- Increases lipogenesis
- Decreases lipolysis
- Promotes triglyceride storage
Result
- Fat accumulation
- Energy storage
3. Effects On Protein Metabolism
Insulin is anabolic.
Actions
- Increases amino acid uptake
- Increases protein synthesis
- Decreases protein breakdown
4. Effects On Electrolytes
- Increases K⁺ entry into cells
- Promotes phosphate uptake
Overall Metabolic Effects
|
Metabolism |
Effect of Insulin |
|
Carbohydrate |
↓ Blood glucose |
|
Protein |
↑ Protein synthesis |
|
Fat |
↑ Fat storage |
|
Electrolytes |
↑ K⁺ uptake |
Glucose Homeostasis
Blood glucose is regulated jointly by:
- Insulin
- Glucagon
Fed State
- Insulin dominates
- Glucose stored
Fasting State
- Glucagon dominates
- Glucose released
INSULIN AND GLUCAGON: COMPARISON
|
Feature |
Insulin |
Glucagon |
|
Secreted by |
β-cells |
α-cells |
|
Nature |
Peptide hormone |
Peptide hormone |
|
Blood glucose |
Decreases |
Increases |
|
Action |
Hypoglycemic |
Hyperglycemic |
|
Glycogenesis |
Stimulates |
Inhibits |
|
Glycogenolysis |
Inhibits |
Stimulates |
Diabetes Mellitus
Definition
A metabolic disorder characterized by:
- Hyperglycemia
- Glucose in urine
- Impaired insulin secretion/action
Types of Diabetes Mellitus
Type 1 Diabetes Mellitus- Insulin Dependent Diabetes Mellitus (IDDM)
Cause
- Autoimmune destruction of β-cells
- Absolute insulin deficiency
Features
- Usually in children
- Requires insulin therapy
Type 2 Diabetes Mellitus- Non Insulin Dependent Diabetes Mellitus (NIDDM)
Cause
- Insulin resistance
- Relative insulin deficiency
Features
- Common in adults
- Associated with obesity
Symptoms of Diabetes
Classical Symptoms
3 Ps
- Polyuria
- Polydipsia
- Polyphagia
Other symptoms:
- Weight loss
- Fatigue
- Blurred vision
Complications of Diabetes
Acute
- Diabetic ketoacidosis
- Hypoglycemia
Chronic
- Retinopathy
- Nephropathy
- Neuropathy
- Cardiovascular disease
Diabetic patients can be treated successfully using insulin.
Routes
- Usually subcutaneous injection
Types of Insulin
|
Type |
Onset |
|
Rapid acting |
Minutes |
|
Short acting |
30–60 min |
|
Intermediate acting |
Hours |
|
Long acting |
Prolonged |
Hypoglycemia
Definition
Low blood glucose level due to excess insulin.
Symptoms
- Sweating
- Tremors
- Hunger
- Confusion
- Coma (severe)
Important Points
- Insulin is secreted by β-cells
- Insulin is a protein hormone
- Insulin decreases blood glucose
- Insulin promotes glycogenesis
- Glucagon is antagonistic to
insulin
- C-peptide released with insulin
- Insulin deficiency causes
diabetes mellitus
- GLUT-4 transporters increase
glucose uptake
- Insulin acts via tyrosine kinase
receptor
High-Yield Flowchart
High Blood Glucose
↓
β-cells stimulated
↓
Insulin secretion
↓
Glucose uptake by tissues
↓
Glycogenesis + Lipogenesis
↓
Decrease in Blood Glucose
Quick Revision Table
|
Feature |
Insulin |
|
Secreted by |
β-cells |
|
Nature |
Peptide hormone |
|
Amino acids |
51 |
|
Main action |
Lowers blood glucose |
|
Receptor |
Tyrosine kinase |
|
Deficiency |
Diabetes mellitus |
|
Opposite hormone |
Glucagon |
One-Line Summary
“Insulin is an anabolic peptide hormone secreted by pancreatic β-cells
that lowers blood glucose by promoting uptake and storage of glucose.”
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