Insulin Storage and Release
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Transcript of Insulin Storage and Release
STORAGE AND RELEASE OF INSULIN
Presented By SRI ADITYA KOTAMRAJU
Seminar on
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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 INSULINInsulin 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 INSULINBasically 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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MECHANISM OF ACTION
INSULIN SECRETION
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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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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.
STORAGE OF COMMERCIAL INSULIN
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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 observed1.Appearance2.Sterility and bacterial endotoxin content3.Particular matter and ph
4.Insulin glargine and noninsulin glargine content5.Preservative content and stability6.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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