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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