Seminar on

STORAGE AND RELEASE

OF INSULIN

Presented By
SRI ADITYA KOTAMRAJU

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 INTRODUCTION

The islet of Langerhans is

composed of four types of
cells.
They are
α-cells –Glucagon
β-cells –Insulin
Δ-cells –Somatostatin
F-cells –Pancreatic
polypeptide

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 SYNTHESIS OF INSULIN
Insulin is synthesized in β-cells by the usual cell
machinery for protein synthesis, beginning with
translation of insulin RNA by ribosomes to form an
insulin preprohormone.
The signal sequence is required for association
and penetration of nascent preproinsulin in to
lumen of endoplasmic reticulum.
The preprohormone is then cleaved in
endoplasmic reticulum to form proinsulin.
Most of it is further cleaved in the Golgi complex
to form insulin and C-peptide.
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In solution, insulin can exist as a monomer,
dimer, or hexamer.
It is believed that Zn2+ has a functional role in the
hexamer formation and that this process facilitates
the conversion of proinsulin to insulin and storage
of the hormone.

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Insulin is synthesized from the proinsulin precursor
molecule by the action of proteolytic enzymes,
known as prohormone convertases (PC-1 & PC-2)
as well as the exoprotease Carboxypeptidase E

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 SECRETION OF INSULIN
Basically the resting b- cell is hyperpolarised and its depolarisation
leads to the secretion of insulin.

SEQUENCE OF STEPS INVOLVED:

Glucose enters  through the glucose transporter GLUT2.

 GLYCOLYSIS
 
  ATP molecules are produced

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  ATP controlled Potassium channels (K+) CLOSE

Voltage controlled calcium channelas (Ca2+) open

Phosphotidyl inositol 4,5 bisphasphate 

Inositol 1,4,5-triphosphate (IP3)

Release of Ca2+via IP3 gated channels

Release of previously synthesized insulin

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CHEMISTRY
 INSULIN SECRETION

MECHANISM OF ACTION

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REGULATION OF INSULIN SECRETION:

 Glucose, amino acids, fatty acids, and ketone bodies

promote the secretion of insulin.
 Stimulation of a2 adrenergic receptors inhibits insulin
secretion, whereas b2 adrenergic receptor agonists
and vagal nerve stimulation enhance release.
 Several gastrointestinal hormones promote the
secretion of insulin. These are gastrointestinal
inhibitory peptide (GIP) and glucagonlike peptide 1
(GLP-1).
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Insulin release also is stimulated by gastrin, secretin,
cholecystokinin, gastrin-releasing peptide, and
enteroglucagon.

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Insulin secretion is Biphasic
Phase -1: Concentration
reaches a peak after
1-2 minutes and is short
lived.
Phase -2: Delayed onset
but for longer duration

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 STORAGE OF COMMERCIAL INSULIN
The individual manufacturer’s storage recommendations
and expiry dates must be adhered to. These usually
suggest that
• Insulin must never be frozen.
• Direct sunlight or warming (in hot climates) damages
insulin.
• Unused insulin should be stored in a refrigerator
(2–8°C)
• After opening, an insulin vial should be discarded after
3 months if kept at 2–8°C or after 1 month if kept at
room temperature.
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• In hot climates where refrigeration is not available,
cooling jars or a cool wet cloth around the insulin will
help to preserve the insulin activity.

ANALYTICAL PROCEDURES:
The following parameters are to be observed
1.Appearance
2.Sterility and bacterial endotoxin content
3.Particular matter and ph
4.Insulin glargine and noninsulin glargine content
5.Preservative content and stability
6.Photo stability

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 DEGRADATION OF INSULIN
• Degradation of insulin occurs primarly in liver, kidney
and muscle. About 50% of insulin that reaches liver
via portal vein is destroyed and never reaches
general circulation.
• The complex of insulin and its receptor is internalised
in to endosomes. Some insulin is also delivered to
lysosomes for degradation.
• Several enzymes have been implicated, primarly
insulin degrading enzyme which is thiol
metalloproteinases. It is localised in hepatocytes.

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INSULIN DEGRADING ENZYME:
 It is also known as Insulysin or Insulin Protease.
 IDE is a large zinc binding protease of metelloprotease
subfamily known to cleave multiple short peptides.
IDE and Alzheimers disease:
 According to amyloid hypothesis causative agent for
alzheimers disease is hydrophobic peptide amyloid
beta.
 IDE can degrade Amyloid Beta (AB), a peptide
implicated in pathogenesis of Alzheimers disease.

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 REFERENCES
• WILSON AND GISVOLDS 11TH EDITION
• MEDICINAL CHEMISTRY BY FOYE
• GOODMAN AND GILMANS 11th EDITION
• PHARMACOLOGY BY RANG and DALE 5th EDITION
• http://care.diabetesjournals.org/content/26/9/2665.full
• http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/
pancreas/insulin.html
• http://jb.oxfordjournals.org/cgi/content/abstract/72/1/157

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