Introduction to Diabetes Mellitus: Insulin Action Flashcards
How does insulin affect Glucose, protein and lipid?
- Glucose: decrease hepatic glucose output
- Protein: decreased proteolysis
- Lipid: decrease lipolysis, and decrease ketogenesis
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 GLUT-4 work
Insulin stimulates Glucose transporter 4.
It has hydrophobic elements on the outside embedded in the membrane and a hydrophilic core which allows glucose into the cell.
It sits in vesicles within the cytoplasm. Insulin recruits them to the membrane causing glucose uptake.
How does insulin affect proteolysis?
Inhibits proteolysis
- amino acids can be oxidised in the muscle cell and insulin prevents this oxidation.
- insulin increases the re-synthesis of proteins from amino acids.
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 and protein synthesis is stimulated by insulin.
What do gluconeogenesis and glycogenolysis in the liver contribute towards?
What increases gluconeogenesis?
What inhibits gluconeogenesis?
Glucose produced enters circulation as Hepatic Glucose Output
Insulin inhibits gluconeogenesis.
Somatotrophin, cortisol, catecholamines and glucagon increase gluconeogenesis.
How do triglycerides enter adipocytes?
Triglycerides must be broken down by LIPOPROTEIN LIPASE before they can enter the adipocyte.Insulin stimulates Lipoprotein Lipase.
TAGs are broken down by lipoprotein lipase to:
Glycerol and
Non-Esterified Fatty Acids (NEFA) which are absorbed by the adipocyte
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 a fatty acid 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 does the adipocyte in the gut show.
What is an indicator for ischaemic heart disease
- the adipocyte is different in activity and endocrine regulation.
- the omental fat/waist circumference is a simple indicator of someones risk of ischaemic heart disease.
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 by adding 2 glycerols, 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 acyl coA to ketone bodies
Glucagon promotes the conversion of fatty acyl coA 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 in muscle cells (because it is trying to increase blood glucose so one way of doing this is by decreasing uptake)
what happens in the fed state compared to fasted state
Fasted:
Low insulin: glucagon ratio.
-brain uses glucose then ketone bodies
-muscle uses fat
increase in:
conc of NEFA, proteolysis, lipolysis, hepatic glucose output
decrease in:
amino acid conc
Fed state:
high insulin: glucagon ratio.
-stored insulin released during 2nd phase
-stop hepatic glucose output
increase in:
glycogen, protein synthesis, lipogenesis
decrease in:
gluconeogeneis, proteolysis
What is the usual presentation of Type 1 Diabetes Mellitus?
Polyuria Polydipsia Glycosuria (lots of glucose in your urine) with osmotic symptoms Proteolysis with weight loss Ketonuria
What is used as a treatment for insulin induced hypoglycaemia?
Intramuscular glucagon as it triggers an increase in HGO
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.
-glucose and ketones are high in T1DM
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
What happens to fatty acids generated from lipolysis?
Enter liver and used to make ketone bodies
What happens to the ketone bodies?
Enter circulation and used by muscles
What is insulin induced hypoglycemia? What does it increase and decrease?
Glucose enters cells Increase in: - Insulin (given this to cause hypoglycemia) - Glucagon - Catecholamines - Cortisol - Somatotrophin ( growth hormone)
Decrease in:
- HGO
- Lipolysis
What is subcutaneous insulin involved in?
Switching off HGO.
subcutaneous insulin is involved in switching off HGO(Hepatic Glucose Output)
Why is heart disease common in people with diabetes?
Increase in LDL (Dyslipidaemia)
- Causes damage to the blood vessels leading to heart attacks
What is the effect of insulin resistance?
Increase in:
- Circulating NEFA
- Triglyceride
- LDL cholesterol
Decrease in:
- Lipoprotein lipase activity which also results in VLDL clearance
- HDL cholesterol
