Insulin is a peptide hormone produced by beta cells of the pancreatic islets, and it is considered to be the main anabolic hormone of the body. It regulates the metabolism of carbohydrates, fats and protein by promoting the absorption of, especially, glucose from the blood into fat, liver and skeletal muscle cells.

1. INSULIN
BY
Dr. Muhammad Saifullah
Punjab Medical College, Faisalabad

2. PANCREAS - INTRODUCTION
• The pancreas is the largest of the digestive glands
present inside the abdominal cavity.
• The pancreas, in addition
to its digestive functions,
secretes two important
hormones, insulin and
glucagon, that are crucial
for normal regulation of
glucose, lipid, and protein
metabolism.

3. HISTOLOGY OF THE PANCREAS
The pancreas is composed
of two major types of
tissues:
• Acini, which secrete
digestive juices into the
duodenum.
• Islets of langerhans,
which secrete insulin
and glucagon directly
into the blood.

4. INSULIN
Insulin is a small
protein; human
insulin has a
molecular weight of
5808. It is composed
of two amino acid
chains, connected to
each other by
disulfide linkages.

5. INSULIN RECEPTOR
The insulin receptor is a combination of four
subunits held together by disulfide linkages:
 Two alpha subunits that lie entirely
outside the cell membrane
 Two beta subunits that penetrate
through the membrane, protruding into
the cell cytoplasm.
NOTE: The insulin binds with the alpha
subunits on the outside of the cell.

7. SYNTHESIS OF INSULIN
 Insulin is synthesized in the pancreas
within the β-cells of the islets of
Langerhans.
 The endocrine portion accounts for only
2% of the total mass of the pancreas.
 Within the islets of Langerhans, beta cells
constitute 65–80% of all the cells.

8. SYNTHESIS OF INSULIN
Proinsulin
(ER)
Immature
granules
(Golgi
complex)
Insulin + C-
peptide
(Golgi
complex)
Mature
granules
(Active
Insulin)
Insulin ready
to be
released,
(Plasma half
life 6 min)
Pancreatic β-
cells (RER)
Preproinsulin
synthesis

9. METABOLIC EFFECTS OF INSULIN
• Effect on Carbohydrate Metabolism
• Effect on Fat Metabolism
• Effect on Protein Metabolism & Growth

10. EFFECT ON CARBOHYDRATE METABOLISM
• Insulin promotes muscle glucose uptake and
metabolism between meals.
• Storage of glucose as glycogen in non-
exercising muscle.
• Insulin promotes liver uptake & storage of
glucose as glycogen after the meal which is
later released back when required.

11. EFFECT ON CARBOHYDRATE METABOLISM
• Insulin promotes conversion of excess
glucose into fatty acids and inhibits
gluconeogenesis in the liver.
• Lack of effect of insulin on glucose uptake
and usage by the brain because brain cells
can use glucose even without insulin.
• In other cells insulin increases glucose
transport into and glucose usage by most
other cells of the body.

12. EFFECT ON FAT METABOLISM
• Insulin promotes fat synthesis.
• Insulin promotes storage of fat in the adipose
cells.
• Insulin deficiency causes lipolysis of storage
fat and release of free fatty acids which is
used for energy.
• Insulin deficiency increases plasma
cholesterol and phospholipid concentrations.

13. EFFECT ON PROTEIN METABOLISM & GROWTH
• Insulin promotes protein synthesis and
storage by stimulating transport of many of
the amino acids into the cells and promoting
translation of mRNA.
• Insulin deficiency causes protein depletion
and increased plasma amino acids.
• Insulin and growth hormone interact
synergistically to promote growth because it
is anabolic hormone.

14. MECHANISM OF INSULIN SECRETION
GLUT-2 allows
glucose entry into
the β-cells of
Pancreas
Glucose
phosphorylated
into glucose-6-
Phosphate
ATP formation occurs
which Inhibits ATP-
sensitive Potassium
Channels
Depolarization of
the cell Membrane
occurs which opens
voltage-gated
Calcium channels
Calcium Influx
causes Insulin
vesicles to fuse
with cell
membrane
Insulin
secreted into
ECF by
Exocytosis
Increased
blood glucose

16. FACTORS AFFECTING INSULIN SECRETION
INCREASE INSULIN SECRETION DECREASE INSULIN SECRETION
1. Increased blood glucose
2. Increased blood free fatty acids
3. Increased blood amino acids
4. Gastrointestinal hormones
(gastrin)
5. Glucagon, growth hormone,
cortisol
6. Parasympathetic stimulation;
A.Ch
7. β-Adrenergic stimulation
8. Sulfonylurea drugs (glyburide,
tolbutamide)
1. Decreased blood glucose
2. Fasting
3. Somatostatin
4. Alpha-Adrenergic activity
5. Leptin

18. ABNORMALITIES RELATED TO INSULIN:
INSULINOMA:
 Pancreatic β-cell tumour
 Characterized by recurrent hypoglycemia.
 Usually small tumour (<5mm in Dia)
 10% Malignant
 Diagnosed by CT-scan, MRI or Ultrasound
 Treatment:
Medical: Diet control + Insulin inhibitors
(Diazoxide)
Surgical: Resection

19. DIABETES MELLITUS
• Clinical syndrome characterized by hyperglycemia
due to absolute or relative deficiency of Insulin.
• Types
I. Type I – IDDM is usually due to
autoimmune disease leading to β-cell
destruction.
II.Type II – NIDDM is due to relative Insulin
deficiency due to Insulin resistance and
impaired β-cell dysfunction.

20. COMPLICATIONS OF DIABETES:
• Microvascular:
1. Retinopathy
2. Nephropathy
3. Diabetic foot
• Macrovascular:
1. Myocardial infarction
2. Cerebral infarction
3. Peripheral vascular Ischemic disease
MANAGEMENT:
Strict diabetic control via:
1. Diet
2. Drugs
3. Exercise

21. REFERENCES
• Guyton and Hall Textbook of Medical
Physiology 12th edition
• Davidson's Principles and Practice of Medicine
• Wikipedia, the free encyclopedia