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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
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!
GLUCAGON
SYNTHESIS: in the alpha cells of the Islets of Langerhans.
Preproglucagon (158 AA)↓
Glucagon + Major proglucagon fragment(in the alpha cells)
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.
ACTIONS OF GLUCAGON
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.
Mechanism of GlycogenolysisGlucagon 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
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.
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.
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
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 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.
Glucagon Dominates in Fasting State Metabolism
Figure 21-14: Endocrine response to hypoglycemia
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”.
Glycogen Glucose Pyruvate
Muscle: Fed State
Glucose from circulation
(Active muscle)
(Inactive muscle)
Glycogen Glucose Pyruvate
Muscle: Fasting State
Acetyl CoAFatty Acids and Ketone Bodiesfrom Circulation
1st uses own glycogen stores2nd absorbs fatty acids and ketone bodies
Glycogen Glucose Pyruvate
Liver: Fed State
Glucose from circulation
Acetyl CoAFatty Acids released to Circulation
Glycogen Glucose Pyruvate
Adipose: Fed State
Glucose from circulation
Acetyl CoAFatty Acids
Fatty Acids fromCirculation
Triacylglycerol(Fat)
Glycogen Glucose Pyruvate
Adipose: Fasting State
Acetyl CoAFatty Acidsand glycerol
Fatty Acids and glycerolreleased to circulation
Triacylglycerol(Fat)
SOMATOSTATIN
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
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!