Transcript glucagon - MBBS Students Club

 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!
 SYNTHESIS:
in the alpha cells of the Islets of
Langerhans.
Preproglucagon (158 AA)
↓
Glucagon + Major proglucagon fragment
(in the alpha cells)
 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.
The physiological role of Glucagon is to stimulate
hepatic production & secretion of glucose. It
accomplishes this by:
1.
Glycogenolysis
2.
Increased Gluconeogenesis
NOTE:
 Muscle DOES NOT respond to Glucagon.
 It exerts its effects on the Liver and Adipose tissues.
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
 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.
 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.
 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
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, insulinstimulated glucose uptake increases, and plasma
glucose concentrations fall.
 Unless something counteracts this process, the brain’s
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.

Figure 21-14: Endocrine response to hypoglycemia
 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”.
Muscle: Fed State
Glucose from circulation
(Active muscle)
Glycogen
Glucose
(Inactive muscle)
Pyruvate
Muscle: Fasting State
1st uses own glycogen stores
2nd absorbs fatty acids and ketone bodies
Glycogen
Glucose
Fatty Acids and Ketone Bodies
from Circulation
Pyruvate
Acetyl CoA
Liver: Fed State
Glucose from circulation
Glycogen
Glucose
Fatty Acids released to Circulation
Pyruvate
Acetyl CoA
Adipose: Fed State
Glucose from circulation
Glycogen
Triacylglycerol
(Fat)
Glucose
Pyruvate
Fatty Acids
Acetyl CoA
Fatty Acids from
Circulation
Adipose: Fasting State
Glycogen
Glucose
Fatty Acids
and glycerol
Pyruvate
Acetyl CoA
Triacylglycerol
(Fat)
Fatty Acids and glycerol
released to circulation
 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
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!