Presented By

Sohail Amjad
 Hormones

 Hormones are the chemical messengers needed in small
amount just to inhibit or accelerate the metabolic pathways of
the target organs.

Classification
1. Proteins and polypeptides:
 Including hormones secreted by the anterior and posterior pituitary
gland,
 the pancreas (insulin and glucagon), the parathyroid gland
(parathyroid hormone).
2. Steroids:
Naturally occurring compounds which are responsible for
manufacturing and maintenance of reproductive systems.
• Secreted by the adrenal cortex (cortisol and aldosterone),
• the ovaries (estrogen and progesterone),
• the testes (testosterone)

3.Derivatives of the amino acid:

secreted by the
• thyroid (thyroxine and triiodothyronine)
• adrenal medullae (epinephrine and norepinephrine).
 INSULIN

 Insulin is a peptide hormone secreted by the β cells
of the pancreatic islets of Langerhans and maintains
normal blood glucose levels by facilitating cellular
glucose uptake, regulating carbohydrate, lipid and
protein metabolism .
 Islets of Langerhans

These are clusters of cells that are embedded in the endocrine portion
of the pancreas.
Islets of Langerhans comprises of 4 types of cells.
 Alpha cells Glucagon
 Beta cells Insulin
 Delta cells Somatotrophine
 F cells Aids in digestion

Also called as
Pancreatic Polypeptide
Islets of Langerhans
 Structure of insulin
•

Normal insulin that is biologically active is monomeric or
exists as a single molecule. It has two long amino acid
chains or polypeptide chains. The chains are chain A with
21 amino acids and chain B with 30 amino acids.

• Two disulfide bridges (residues A7 to B7, and A20 to B19)

covalently connect the chains, and chain A contains an
internal disulfide bridge (residues A6 to A11). These joints
are similar in all mammalian forms of insulin.
Structure of insulin
When secreted insulin joins in two’s to form dimmers and
then in six’s to form hexamers. This combination takes place
in the presence of zinc

Three Dimensional view of Insulin

• The peptide chains then form 2 dimensional and three
dimensional forms. Each of these 3-dimensional structures
have three helices and three conserved disulfide bridges. This is
a basic fold. This basic fold is present in all members of the
insulin peptide family.

• At the core or center of the molecules is a hydrophobic or

“water-hating” or water repellent area. These cluster of
hydrophobic residues in the center contributes to protein
stability. Stability is also lent by the disulfide bridges.

• Surrounding its core, the monomer has two extensive nonpolar

surfaces. One of them is a flat one that is aromatic and gets
buried when there is a dimer formation. The other surface is
more extensive and disappears when a hexamer is formed. This
is called the quaternary structure of insulin.
Three Dimensional structure of Insulin
Biosynthesis of insulin

 Biosynthesis involves production of two inactive
precursors , preproinsulin and proinsulin , that are
sequentially cleaved to form the active hormone plus the
connecting or C-peptide.
C-peptide:
1. The C -peptide e is essential for proper insulin folding
 Bio-Synthesis of insulin
It basically involve some steps
1. Formation of precursors
 preproinsulin
 proinsulin
2. Transportation through golgi apparatus
3. Formation of granules
4. Exocytosis from the cell
5.Formation of insulin alongwith connecting or C
peptide
Diagram of Synthesis of Insulin
 Secretion of Insulin

 Insulin is secreted by Pancreatic-Beta cells in response to
increased blood Glucose concentration.
 The beta cells have a large number of glucose transporters
(GLUT2)that permit a rate of glucose influx that is proportional
to the blood concentration in the physiologic range.
 Once inside the cells, Glucose is phosphorylated to glucose-6-
phosphate by glucokinase.
 The glucose-6-phosphate is subsequently oxidized to form
(ATP), which inhibits the ATP-sensitive potassium channels of
the cell.
 Closure of the potassium channels depolarizes the cell
membrane, thereby opening voltage-gated calcium channels.
 This produces an influx of calcium that stimulates fusion of the
docked insulin-containing vesicles with the cell membrane and
secretion of insulin into the extracellular fluid by exocytosis.
 Mechanism of Action of
Insulin

 Insulin Receptors on Plasma membrane of Cell
 Action of insulin on following cells
Skeletal Muscle cells
Liver cells
Adipocytes
Animation to understand the
action of Insulin

 Regulation of Insulin

Insulin secretion is increased by following factors:

1. Blood glucose level

2. Amino acids
3. Gastrointestinal peptide hormones
Role of blood glucose level :

 As the concentration of blood glucose rises above normal value , the

rate of insulin secretion rises rapidly.

 The insulin in turn increases transport of glucose into liver and

muscle , thereby reducing the blood glucose concentration back
toward the normal value
Amino acids:
 The excess amino acids in the blood also stimulate insulin secretion.

 The potent amino acids are arginine and lysine.

 Amino acids alone can cause a slight increase.

Gastrointestinal Hormones:
 Gastrin , secretin , cholecystokinin, and gastric inhibitory
peptide (causes a moderate) increase in insulin secretion.

 They act the same way as amino acids increase insulin secretion.
Inhibition of insulin secretion

The insulin secretion is inhibited :

1. By stimulation of sympathetic nerves.

 Neurotransmitter i.e non adrenaline.

2. By the stimulation of somatostatin hormone.

Metabolic Effects of
Insulin
• On Carbohydrates
• On Lipids
• On Proteins Synthesis
 On Carbohydrates metabolism
Promote its storage and are most prominent in three tissues….

In liver and muscle, increases glycogen synthesis……

In muscle and adipose tissue, increase glucose uptake by

increasing the number of glusose transporters…

In liver, insulin decreases production of glucose….by inhibition of

glycogenolysis and gluconeogenesis
 On lipid metabolism
 Rise in insulin cause sufficient reduction in the release of Fatty
acids from adipose tissue by inhibiting the activity of hormone-
sensitive lipase, a key enzyme of TAG degradation in
adipocytes.
 Acting by promoting the dephosphorylation and, hence,
inactivation of enzyme.
 Also increase the transport and metabolism of glucose into
adipocytes, providing the glycerol 3-phosphate substrate for
TAG synthesis.
 Insulin also promotes the conversion of glucose to TAG in liver.
The TAG are secreted in VLDL.
 On protein synthesis
Stimulates entry of amino acids into cells…..
Stimulates protein synthesis….through….
Transcription of DNA
Translation of mRNA
•Inhibits catabolism of Protein….amino
acids….Gluconeogenesis……Glucose produced….
Glycogenolysis:

The breakdown of glycogen into glucose in muscles and liver.

Gluconeogensis:

The formation of glucose from amino acids.

 Diseases

Diabetes

Diabetes Type 1

 where the body's immune system attacks and destroys

the cells that produce insulin.
 Type 1 diabetes can develop quickly over weeks or even
days.
Diabetes Type 1

 Diabetes type 2

where the body doesn't produce enough insulin, or the
body's cells don't react to insulin
Trend in the rise of diabetic patients in Pakistan.

 Pakistan has over 7 million diabetic patients; 84,000 die every year due
to diabetes of which majority are women. Studies reveal that Pakistan
ranks 7th among the top 10 countries with the highest number of people
living with diabetes: experts
 Symptoms
 feeling very thirsty
 urinating more frequently than usual, particularly at night
 feeling very tired
 weight loss and loss of muscle bulk
 cuts or wounds that heal slowly
 blurred vision

Pharmacologic Treatment
2 types of treatment

Noninsulin Insulin
Therapies Therapies
 References
 World Health Organization. Obesity: Preventing and
Managing the Global Epidemic Report of a WHO Consultation
Technical Report Series. World Health Organization, Geneva
2000. [PubMed]
 Shaw J, Sicree R, Zimmet P. Global estimates of the prevalence
of diabetes for 2010 and 2030. Diab Res Clin
Practice. 2010;87(1):4–14. doi:
10.1016/j.diabres.2009.10.007. [PubMed]
 3Denton RM, Tavaré JM. Molecular basis of insulin action on
intracellular metabolism. In: Alberti KGMM, Zimmet P,
Defronzo RA, Keen H (Hon), editors. International Textbook of
Diabetes Mellitus (2nded) John Wiley & Sons, New York; 1997 p.
469–88.
 Text Book Of Medical Physiology By Guyton and Hall
 Biochemistry by Lipponcott