Introduction to Diabetes Mellitus: Insulin Action Flashcards
In which tissues is Glut-4 usually found?
Most glucose uptake is via Glut-4
It is particularly abundant in MUSCLE and ADIPOSE tissue
How is Glut-4 different to Glut-2?
Glut-4 is insulin responsive whereas Glut-2 isn’t
How does insulin affect proteolysis?
Inhibits proteolysis
How does cortisol affect proteolysis?
Promotes proteolysis (cortisol is a stress hormone that is concerned about increasing blood glucose)
What effect does glucagon have on uptake of amino acids by the liver?
Increases uptake of amino acids by the liver
What do gluconeogenesis and glycogenolysis in the liver contribute towards?
Hepatic Glucose Output
How do triglycerides enter adipocytes?
Triglycerides must be broken down by LIPOPROTEIN LIPASE before they can enter the adipocyte.
TAGs are broken down by lipoprotein lipase to:
Glycerol
Non-Esterified Fatty Acids (NEFA)
How is glucose converted to triglycerides?
Glucose can be converted to NEFA
Glucose can also be chopped in half to produce glycerol
They can then be stuck together to make triglycerides
How are the effects of insulin in the blood different to insulin in adipocytes?
Blood - insulin promotes the breakdown of triglycerides (so that they can enter the adipocytes)
Adipocytes - insulin promotes the formation of triglycerides so that they can be stored
What are the two ways in which glycerol can be used by the liver?
Glycerol can be used to make TRIGLYCERIDES for storage
Glycerol can be used to make GLUCOSE that supports hepatic glucose output
What are the three main ketone bodies?
Acetone
Acetoacetate
3-hydroxybutyrate
What are the effects of insulin and glucagon on fatty acid metabolism?
Insulin inhibits the conversion of fatty acids to ketone bodies
Glucagon promotes the conversion of fatty acids to ketone bodies
What does a high blood glucose and high ketone bodies indicate?
Insulin Deficient
Explanation: Insulin promotes uptake of glucose from the blood and inhibits conversion of fatty acids to ketone bodies
So…
High blood glucose and high ketone bodies must mean that they are INSULIN DEFICIENT
When are ketone bodies produced?
Produced at times of LOW FOOD INTAKE or CARBOHYDRATE RESTRICTION
How do insulin, catecholamines and glucagon affect glycogenolysis?
Insulin - promotes STORAGE of glucose as glycogen
Catecholaines and Glucagon - promote the break down of glycogen to produce glucose (promote glycogenolysis)
What effect do stress hormones have on the uptake of glucose by muscle cells?
Stress hormones inhibit the uptake of glucose via Glut-4 (because it is trying to increase blood glucose so one way of doing this is by decreasing uptake)
What is the usual presentation of Type 1 Diabetes Mellitus?
Polyuria Polydipsia Nocturia Proteolysis with weight loss Ketonuria
What is used as a treatment for insulin induced hypoglycaemia?
Intramuscular glucagon
Where does insulin resistance lie?
Liver, muscle and adipose tissue
It is not a problem with the insulin or the receptor but instead a problem with the post-receptor pathways
How can you differentiate between T1DM and T2DM?
REMEMBER: insulin inhibits the conversion of fatty acids to ketone bodies
HIGH glucose + HIGH ketone bodies = T1DM
Usually, people with T2DM still produce enough insulin to suppress ketone body production though their blood glucose will be high.
What two pathways does insulin have an effect on?
Metabolic Pathway (PI3K-Akt) Mitogenic Pathway (MAPK)
What is the significance of having two pathways in someone who has insulin resistance?
The feedback loop for insulin is mainly through blood glucose concentration
Someone with some degree of insulin resistance will have produce a compensatory hyperinsulinaemia so that they make enough glucose to maintain normal blood glucose
But this high insulin will still be harming them because it has an INCREASE EFFECT ON THE MITOGENIC (MAPK) PATHWAY
State some characteristic features of insulin resistance.
Hypertension High LDL Low HDL Raised fasting blood glucose High omental fat
