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    Insulin Storage and Release

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    Aditya Kotamraju
    The seminar discusses insulin synthesis, storage, and release. It notes that insulin is synthesized in beta cells from proinsulin and stored in secretory granules. Insulin is released through a regulated pathway involving glucose metabolism, ATP production, ion channel activity, and vesicle fusion. Insulin regulates blood glucose levels and is degraded in the liver, kidney, and muscle by enzymes like insulin degrading enzyme. The storage and analytical testing of commercial insulin is also reviewed.

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    Insulin Storage and Release

    Uploaded by

    Aditya Kotamraju
    79 views18 pages
    The seminar discusses insulin synthesis, storage, and release. It notes that insulin is synthesized in beta cells from proinsulin and stored in secretory granules. Insulin is released through a regulated pathway involving glucose metabolism, ATP production, ion channel activity, and vesicle fusion. Insulin regulates blood glucose levels and is degraded in the liver, kidney, and muscle by enzymes like insulin degrading enzyme. The storage and analytical testing of commercial insulin is also reviewed.

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    The seminar discusses insulin synthesis, storage, and release. It notes that insulin is synthesized in beta cells from proinsulin and stored in secretory granules. Insulin is released through a regulated pathway involving glucose metabolism, ATP production, ion channel activity, and vesicle fusion. Insulin regulates blood glucose levels and is degraded in the liver, kidney, and muscle by enzymes like insulin degrading enzyme. The storage and analytical testing of commercial insulin is also reviewed.

    Copyright:

    Attribution Non-Commercial (BY-NC)
    Download as PPT, PDF, TXT or read online from Scribd
    Download as ppt, pdf, or txt
    79 views18 pages

    Insulin Storage and Release

    Uploaded by

    Aditya Kotamraju
    The seminar discusses insulin synthesis, storage, and release. It notes that insulin is synthesized in beta cells from proinsulin and stored in secretory granules. Insulin is released through a regulated pathway involving glucose metabolism, ATP production, ion channel activity, and vesicle fusion. Insulin regulates blood glucose levels and is degraded in the liver, kidney, and muscle by enzymes like insulin degrading enzyme. The storage and analytical testing of commercial insulin is also reviewed.

    Copyright:

    Attribution Non-Commercial (BY-NC)
    Download as PPT, PDF, TXT or read online from Scribd
    Download as ppt, pdf, or txt
    of 18

    Seminar on

    STORAGE AND RELEASE


    OF INSULIN

    Presented By
    SRI ADITYA KOTAMRAJU

    1
    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

    DEPARTMENT OF PHARMACEUTICAL CHEMISTRY 2


    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.
    3
    DEPARTMENT OF PHARMACEUTICAL CHEMISTRY
    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.

    DEPARTMENT OF PHARMACEUTICAL CHEMISTRY 4


    5
    DEPARTMENT OF PHARMACEUTICAL CHEMISTRY
    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

    DEPARTMENT OF PHARMACEUTICAL CHEMISTRY 6


    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

    DEPARTMENT OF PHARMACEUTICAL CHEMISTRY 7


      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


    DEPARTMENT OF PHARMACEUTICAL
    8
    CHEMISTRY
    INSULIN SECRETION

    MECHANISM OF ACTION

    9
    DEPARTMENT OF PHARMACEUTICAL CHEMISTRY
    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).
    DEPARTMENT OF PHARMACEUTICAL CHEMISTRY 10
    Insulin release also is stimulated by gastrin, secretin,
    cholecystokinin, gastrin-releasing peptide, and
    enteroglucagon.

    DEPARTMENT OF PHARMACEUTICAL CHEMISTRY 11


    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

    DEPARTMENT OF PHARMACEUTICAL CHEMISTRY 12


    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.
    DEPARTMENT OF PHARMACEUTICAL CHEMISTRY 13
    • 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

    DEPARTMENT OF PHARMACEUTICAL CHEMISTRY 14


    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.

    DEPARTMENT OF PHARMACEUTICAL CHEMISTRY 15


    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.

    DEPARTMENT OF PHARMACEUTICAL CHEMISTRY 16


    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

    DEPARTMENT OF PHARMACEUTICAL CHEMISTRY 17


    DEPARTMENT OF PHARMACEUTICAL CHEMISTRY 18

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