Endocrine Control Of Metabolism Flashcards
What are the circulating nutrients that are affected by hormones?
Glucose, fatty acids, amino acids, ketone bodies, lactate
What are the stored nutrients that are affected by hormones?
Glycogen, triglycerides and body proteins
What is the normal plasma glucose concentration?
5 mmol/L
What is the critical plasma glucose level?
<2.5 mmol/L
What happens in hypoglycaemia?
Coma and death
What happens in hyperglycaemia?
Chronic exposure to increase glucose concentrations -> protein damage via non-enzymatic glycation
What are the two phases of metabolism?
Absorptive and fasting
What hormones are involved in the absorptive stage of metabolism?
Insulin
What hormones are involved in the fasting stage of metabolism?
Glucagon, adrenaline, cortisol and GH
What are the two main effects of insulin?
Stimulates nutrient storage and inhibits nutrient release
What are the ways in which insulin stimulates nutrient storage?
- Uptake of glucose by skeletal muscle, adipose and other tissues
- glycogen synthesis in liver, skeletal muscle
- uptake of fatty acids and amino acids
How does insulin inhibit nutrient release?
Inhibits release of glucose from liver (hepatic glucose production)
Inhibits fat and protein breakdown (lipolysis and proteolysis)
What does glucagon stimulate?
Hepatic glucose production
What does adrenaline do?
Stimulates hepatic glucose production and stimulates lipolysis
What is lipolysis?
Fatty acid release from adipose tissue stores
What does GH stimulate?
Hepatic glucose production and lipolysis
What does cortisol do?
Stimulates hepatic glucose production and lipolysis and proteolysis
What are the three metabolic pathways that serve energy storage?
Glycogenesis, lipogenesis and triglyceride synthesis
What is triglyceride synthesis?
Esterification of fatty acids for storage as triglycerides
What are the metabolic pathways serving energy release?
Glycogenolysis, glycogenesis, lipolysis, beta oxidation and ketogenesis
What is ketogenesis?
Production of ketone bodies from acetyl coA
What is beta oxidation?
Fatty acids -> acetyl coA
What is lipolysis?
Release of fatty acids from triglyceride breakdown
What is gluconeogenesis?
Synthesis of glucose from non-carb substances
What does glucagon stimulate?
Glycogenolysis and gluconeogenesis
What hormones stimulates lipolysis?
Adrenaline and GH
What is a decrease in plasma glucose sensed by?
Pancreatic islet cells and CNS
What do the pancreatic islet cells do if plasma glucose levels decrease?
Alpha cells secrete glucagon to increase glucose production
What happens when the the CNS senses plasma glucose decrease?
Increase sympathetic flow to the liver, pancreas and chromaffin cells
What do chromaffin cells do when activated?
Release adrenaline that stimulates pancreatic alpha cells and liver
What are the short term defences against hypoglycaemia?
Glucagon, adrenaline and SNS
What are the medium term defences against hypoglycaemia?
Ketogenesis
What are the long term defences against hypoglycaemia?
Cortisol stimulates proteolysis to supply amino acid substrates for gluconeogenesis
What are the defences against hyperglycaemia?
Insulin
How does insulin defend against hyperglycaemia?
Stimulates glucose uptake by tissues and inhibits hepatic glucose production
What is type 1 diabetes mellitus?
Complete insulin deficiency
What is type 2 diabetes mellitus?
Insulin insufficiency combined with resistance
What are the main insulin sensitive tissues in the body?
Liver, skeletal muscle and adipose tissue
Why is the liver insulin sensitive?
Maintains [plasma glucose]
Why is skeletal muscle insulin sensitive?
Buffers rise in [plasma glucose]
Why is adipose tissue insulin sensitive?
Store dietary fats/ excess glycogen
What’s special about adipocytes?
They have a large fat droplet that occupies most of the cell volume
How do TGs enter a cell?
Broken down into fatty acids by lipoprotein lipase and then re-Esterified once inside the adipocyte
How are TGs transported?
Either as chylomicrons or VLDLs
What is lipoprotein lipase stimulated by?
Insulin
What is GLUT4 dependant on?
Insulin
What is hormone sensitive lipase stimulated by?
Adrenaline and noradrenaline
What enzymes break down stored TGs?
Hormone sensitive lipase
What is glycerol used for in the liver?
Gluconeogenesis
What processes break down fatty acids?
Beta oxidation or ketogenesis
How can glucose be taken up in muscle?
GLUT4 receptors or muscle contraction
When are fatty acids used for energy in muscle?
Endurance exercise
Where is glucose metabolism directed with high insulin and low glucagon?
Towards glycogen storage
Where are amino acids directed with low insulin and high glucagon?
Away from protein synthesis and into glyconeogenesis
Where can acetyl CoA be used?
TCA cycle or ketogenesis
What is malonyl CoA?
First intermediary in lipogenesis
What does malonyl coA inhibit (and how)?
Fatty acyl coA -> keto acids
Blocking the movement of fatty acyl CoA into mitochondria by blocking CPT (a transporter)
What can ketone bodies cause at high concentrations?
Acidosis
What is ketone body-induced acidosis usually buffered by?
HCO3-
How does diabetic ketoacidosis happen?
In the absence of insulin, gluconeogenesis, lipolysis and beta oxidation are unregulated so increase
What happens if gluconeogenesis, lipolysis and beta oxidation is unregulated?
Oxaloacetate from TCA cycle being used up in gluconeogenesis so not combined with acetyl CoA and so acetyl CoA builds up
What happens to the built up acetyl coA when there’s no insulin present?
Funnelled into ketogenesis and increase in [acetate] and [hydroxybutyrate]
