Insulin counter-regulatory hormones Flashcards
Outline the synthesis of glucagon
Preproglucagon is synthesised by the pancreatic alpha cells, this molecule is cleaved to form proglucagon. This proglucagon is then cleaved to form glucagon in the alpha pancreatic cells, or other molecules such as GLP-1 in the brain or L-intestinal cells
What is glucagon secretion stimulated by?
Reduced blood glucose concentration or increase blood amino acids (especially alanine and arginine as glucagon stimulates the synthesis of glucose from these substrates –> gluconeogenesis), and exercise
What is glucagon secretion inhibited by?
Insulin and somatostatin
How does insulin work to inhibit glucagon secretion?
Insulin works to convert cAMP into 5’ AMP via the action of a phosphodiesterase enzyme, and thd therefore glucagon can no longer activate protein kinase A (PKA) and this inhibits glucagon’s mechanism of action
What type of receptor is the glucagon receptor?
G-protein coupled receptor
What are the main actions of glucagon?
Increase glycogenolysis, increased gluconeogenesis, inhibition of glycolysis, increased lipolysis in adipose tissue
What are the main substrates used in gluconeogenesis?
Amino acids, glycerol and lactate
How does glucagon work to encourage gluconeogenesis but inhibit glycolysis?
These processes are effectively the reverse of each other, where the direction of committance is determined by pyruvate kinase (PK) and phosphofructokinase 1 (PFK-1); glucagon inhibits PK and PFK-1 in order to encourage gluconeogenesis and inhibit glycolysis.
How does glucagon work to encourage lipolysis in adipose tissue?
Glucagon activates hormone-sensitive lipase to encourage lipolysis. The glycerol –> glujconeogenesis in the liver whereas the fatty acids can be used in beta oxidation and converted to acetyl CoA
What is the carnitine shuttle?
The carnitine shuttle is responsible for transferring long-chain fatty acids across the barrier of the inner mitochondrial membrane to gain access to the enzymes of beta-oxidation
How does insulin affect the carnitine shuttle, and what is the consequence of this?
The carnitine shuttle is responsible for transferring long-chain fatty acids across the barrier of the inner mitochondrial membrane to gain access to the enzymes of beta-oxidation; the CPT-1 enzyme is a main factor in this shuttle and is inhibited by insulin to prevent acetyl CoA production (ketogenesis substrate)
What enzyme is involved in the transfer of free fatty acids across the inner mitochondrial membrane?
Carnitine shuttle (CPT-1 especially)
How does glucagon affect the carnitine shuttle and what are the consequences of this?
It activates the CPT-1 enzyme and therefore this permits greater amount of beta oxidation and therefore there is more acetyl CoA production and thus greater substrate for ketogenesis.
How does the body facilitate a switch to ketogenesis to prevent excess muscle wasting?
Although there is an increase in free fatty acids as a result of increased lipolysis in adipocytes, beta oxidation of these substrates is prevented by the liver using the oxaloacetate in the mitochondria (from the Krebs cycle) as a substrate for gluconeogenesis; as a result the oxaloacetate:acetyl CoA ratio is reduced, and this leads to an excess of acetyl CoA which can then be used by the liver in ketogenesis.
What are catecholamines?
Adrenaline and noradrenaline
