Introduction To Diabetes Mellitus Flashcards
What are the main actions of insulin?
Glucose: decrease hepatic glucose output, increase muscle uptake (GLUT 4)
Protein: decrease proteolysis
Fat: decrease lipolysis, decrease ketogenesis
What is GLUT-4?
A glucose transporter
Commonly found in myocytes ( muscle) and adipocytes
Highly insulin responsive
Lies in vesicles and is recruited and enhanced by insulin. This leads to a 7 fold increase in glucose uptake
What are the effects of insulin on cell metabolism in myocytes?
Inhibits proteolysis into gluconeogenic amino acids (cortisol stimulates this)
Inhibits mitochondria
Stimulates protein synthesis (so do GH, IGF-1)
What is the effect of insulin on gluconeogenesis in the liver?
Glucagon stimulates the uptake of amino acids into the liver as well as proteolysis and gluconeogenesis (also cortisol)
However the presence of insulin inhibits gluconeogenesis and stimulates protein synthesis
This decreases hepatic glucose output
There is enough glucose present in the blood, no alternate energy sources are needed
Why are other energy sources needed?
In a fasting state, carbohydrate (glucose) stores in liver and muscle will only last 16 hours
So protein and fat and ketone bodies are also needed
What is the effect of insulin on triglycerides and adipose cells?
Insulin binds to LPL (lipoprotein lipase) which breaks down triglycerides into fatty acids (NEFA) and glycerol
These can then leave the blood and enter adipose cells
In the adipocytes these are remade into triglycerides as in the presence of insulin alternate energy sources aren’t needed
Insulin also stimulates the uptake of glucose into adipocytes by GLUT-4. And inhibits the breakdown of triglycerides
GH and cortisol stimulate the breakdown of triglycerides in adipocytes
What happens during gluconeogenesis with fats?
Glycerol is taken up into the liver
This is made into Gly-3P
Depending on need this may be made into triglycerides or undergoes gluconeogenesis to form glucose
What energy sources does the brain use?
Preferably glucose
Some ketone bodies
NOT fatty acids (it is unique in this)
How are ketone bodies made?
In the liver
Fatty Acyl CoA -> acetyl CoA -> acetoacetate -> acetone + 3 OH-B
This goes to ketone bodies
Insulin inhibits this process, glucagon stimulates it
So in a healthy individual you shouldn’t see high levels of glucose and ketone bodies at the same time
What is glycogenolysis?
The generation of glucose from stored glycogen in the liver
This is stimulated by glucagon
What role do muscle cells play in glucose regulation?
Stimulated by insulin they take up glucose
They can form or breakdown glycogen depending
They can also metabolise fatty acids and glucose in the TCA cycle etc to make ATP
The muscle can’t release glucose into circulation
In general what are thinks like in a fasting state?
Low insulin
High glucagon
High conc of fatty acids
Low conc of amino acids (would be high at start but after prolonged fasting they are used up as an energy source)
High proteolysis
High lipolysis
High HGO from gluconeogenesis and glycogenolysis
Muscles used lipids
Brain uses glucose then ketones
Ketogenesis after prolonged fasting
In general what are things like in the fed state?
Stored insulin released (first phase insulin response) then slower release in second phase
High insulin
Low glucagon
No HGO
Glycogen increases
Decreased gluconeogenesis
Increased protein synthesis
Increased lipogenesis
How is diabetes mellitus diagnosed?
Fasting glucose above 7.0 mmol/L
Random glucose above 11.1 mmol/L
Oral glucose tolerance test
HbA1c above 48mmol/mol
Low c peptide
Antibodies GAD and IA2
Presence of ketones
What is type 1 diabetes?
Autoimmune condition
Absolute insulin deficiency (can’t make )
Only type 1 gets ketoacidosis (coz type 3 can still produce insulin)
