GLUCAGON

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GLUCAGON
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GLUCAGON

• Glucagon is secreted when Glucose is GONE
• Peptide hormone made of 29 amino acids.
• MW 3485
• Has several functions that are dramatically
  opposite to Insulin
• One injection of purified glucagon can have
  profound Hyperglycemic effects! Therefore, it is
  also called the HYPERGLYCEMIC HORMONE!

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GLUCAGON

• SYNTHESIS in the alpha cells of the Islets of
  Langerhans.
• Preproglucagon (158 AA)
• ?
• Glucagon Major proglucagon fragment
• (in the alpha cells)

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GLUCAGON METABOLISM

• Circulates without binding to carrier proteins.
• Plasma half-life 5 minutes
• 25 of the Glucagon is destroyed during passage
  through the Liver.
• Glucagon also degraded by the kidneys the
  plasma peptides.

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ACTIONS OF GLUCAGON

• The physiological role of Glucagon is to
  stimulate hepatic production secretion of
  glucose. It accomplishes this by
• Glycogenolysis
• Increased Gluconeogenesis
• NOTE
• Muscle DOES NOT respond to Glucagon.
• It exerts its effects on the Liver and Adipose
  tissues.

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Mechanism of Glycogenolysis

• Glucagon activates adenylyl cyclase in the
  hepatic cell membrane
• ?
• Formation of cyclic adenosine monophosphate
  (cAMP)
• ?
• Protein kinase regulator protein is activated
• ?
• Protien kinase is activated
• ?
• Phosphorylase b kinase is activated
• ?
• Phosphorylase b is converted into phosphorylase a
• ?
• Promotes degradation of Glycogen into
  Glucose-1-phosphate
• ?
• Glucose-1-phosphate is dephosphorylated
• ?
• Glucose is released from the liver

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MECHANISM OF GLUCONEOGENESIS

• It increases the rate of amino acid uptake by the
  liver cells.
• It then stimulates the conversion of many amino
  acids to Glucose.
• ?
• This is achieved by activating many enzymes
  required for AA transport gluconeogenesis.

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OTHER EFFECTS

• It activates adipose cell lipase? increased
  quantities of fatty acids are made available.
• It inhibits storage of TG in the liver ? this
  prevents the liver from removing fatty acids from
  the blood!
• It increases the blood flow in some tissues such
  as kidneys.
• Enhances bile secretion.
• Inhibits gastric acid secretion.

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REGULATION OF GLUCAGON SECRETION

• Increased blood glucose concentration is the most
  potent factor It INHIBITS Glucagon secretion
• Increased amino acids stimulate Glucagon
  secretion (same effect as on INSULIN!)
• Decrease in fatty acid levels stimulate Glucagon
  secretion (opposite to the effect on Insulin).
• Somatostatin inhibits Glucagon Insulin
  secretion
• Exhaustive exercise stimulates Glucagon secretion

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What happens when you take a protein only diet?

• Glucagon release is stimulated by plasma amino
  acids. This pathway prevents hypoglycemia after
  ingestion of a pure protein meal.
• If a meal contains protein but no carbohydrate,
  amino acids absorbed from the food cause insulin
  secretion. Even though no glucose has been
  absorbed, insulin-stimulated glucose uptake
  increases, and plasma glucose concentrations
  fall.
• Unless something counteracts this process, the
  brains fuel supply is threatened by
  hypoglycemia. Co-secretion of glucagon in this
  situation prevents hypoglycemia by stimulating
  hepatic glucose output.
• As a result, although only amino acids were
  ingested, both glucose and amino acids are made
  available to peripheral tissues.

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Glucagon Dominates in Fasting State Metabolism
Figure 21-14 Endocrine response to hypoglycemia
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The Balance b/w insulin Glucagon

• Over-riding concern is glucose homeostasis
• must maintain sufficient levels for use by
  brain
• other tissues adjust to other energy sources as
  necessary.
• Insulin is known as the Hormone of Feasting,
  while Glucagon is known as the Hormone of
  Fasting.

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Muscle Fed State
Glucose from circulation
(Active muscle)
Pyruvate
Glycogen
Glucose
(Inactive muscle)
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Muscle Fasting State
1st uses own glycogen stores 2nd absorbs fatty
acids and ketone bodies
Glycogen
Glucose
Pyruvate
Fatty Acids and Ketone Bodies from Circulation
Acetyl CoA
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Liver Fed State
Glucose from circulation
Pyruvate
Glycogen
Glucose
Acetyl CoA
Fatty Acids released to Circulation
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Adipose Fed State
Glucose from circulation
Pyruvate
Glycogen
Glucose
Acetyl CoA
Fatty Acids
Triacylglycerol (Fat)
Fatty Acids from Circulation
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Adipose Fasting State
Pyruvate
Glycogen
Glucose
Acetyl CoA
Fatty Acids and glycerol
Triacylglycerol (Fat)
Fatty Acids and glycerol released to circulation
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somatostatin
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SOMATOSTATIN

• Secreted by the Delta cells of Islets of
  Langerhans
• Polypeptide containing only 14 AA
• Extremely short half life of 3 minutes
• All matters related to food ingestion increase
  its secretion
• -increased blood Glucose
• -increased fatty acids
• -increased amino acids
• -increased concentrations of GI hormones

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ACTIONS OF SOMATOSTATIN

• It has paracrine function locally within the
  Islets of langerhans where it depresses the
  secretion of both Insulin Glucagon
• It decreases the motility of stomach, duodenum
  gall bladder
• It decreases both secretion absorption in the
  GIT
• Principal role is to extend the period of time
  over which the food nutrients are absorbed into
  the blood by slowing its passage through the GIT!