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Glucagon

 

Glucagon

 Hyperglycemic – Glycogenolytic factor (HGF)

    Produced by α-cells of islets of Langerhans of Pancreas and act antagonistic to insulin

    Involved in 

Rapid mobilization of hepatic glycogen to glucose

    By Glycogenolysis


Chemistry:

    Polypeptide hormone consisting of 29AA

15 different types of amino acids are present

    Unlike insulin no cysteine, proline or isoleucine 

      But tyrosine, methionine and tryptophan are present

      Amino acid sequence is same in all species Molecular wt. of glucagon is approximately 3500 D

    Biosynthesis:

    Synthesized as pro-glucagon in α-cells

    Various peptidases hydrolyse pro-glucagon to glucagon and different inactive peptides

      Carboxy peptidase B

      Trypsin-like peptidase

    Peptidases act on both C – & N – terminals

    Regulation of Secretion:

    Stimulated by 

      low blood glucose level

      Amino acid derived from dietary proteins

      Low levels of epinephrine

    Inhibited by elevated blood glucose level

    Mechanism of Action:

    Act by binding to G-protein coupled receptor on the membranes of hepatocytes and adepocytes

      Activates adenylyl cyclase and increases cAMP

      cAMP then activates protein kinases that regulate the actions of glucagon

    cAMP also induce the synthesis of specific enzymes by increasing transcription of genes

      E.g. Glucose-6-phosphatase enzyme Physiological Functions:

    It influences the metabolism of carbohydrates, proteins and lipids

      Typically acts opposite to insulin

i) Action on carbohydrates metabolism:

    Overall it increases the blood sugar levels

  Cause hyperglycemia

    a) Increases Glycogenolysis in liver only

  Muscle cells lack glucagon receptors

    b) increase gluconeogenesis in liver

  Protein kinase activity leads to the synthesis of new enzymes involved in gluconeogenesis

    PEP carboxykinase

    Pyruvate carboxylase

    Fructose-1,6-bisphosphatase etc.

    c) increase glucogenic aminoacids pool in liver

Increased breakdown and decreased synthesis of proteins

ii) Action on Lipid metabolism:

    a) Promotes lipolysis

  Increase breakdown of TG

  Increased level of FFA

    FA undergo β-oxidation

  Increased formation of ketone bodies

    Thyroid hormones help in lipolytic action of glucagon probably by increasing glucagon receptors on adipocytes

    b) Decreases lipogenesis

  Increased FFA inhibits acetyl-CoA carboxylase

  cAMP phosphorylate acetyl-CoA carboxylase and inactivates it

iii) Action on Protein metabolism:

    a) Reduces protein synthesis

  Decreases the incorporation of AA into peptide chains

  Inactivation of ribosomal components by protein kinases regulated by cAMP

    b) increase amino acid pool in liver for gluconeogenesis

  Stimulate protein catabolism, specially in liver

  Increased uptake of amino acid by liver

    Lowers plasma amino acids level iv) Action on Heart:

  Positive ionotropic effect without myocardial arrhythmias (advantage over nor-epinephrine)

  Increased heart rate and heart contraction

v) Actions on mineral metabolism:

    Increase K+ release from liver

  May be due to glycogenolytic activity

    Decrease plasma Ca2+ levels

  Increase calcitonin release from thyroid gland vi) Calorigenic Actions:

    Increased hepatic de-amination of amino acids

  Thyroid activity is increased to utilize these deaminated residues

  Overall heat of the body increases

    Increase heat production

    Raise basal metabolic rate (BMR)

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