Endocrinology 5 - Diabetes Mellitus Flashcards
How does glucose move into muscle and adipose tissue?
Via the GLUT-4 protein. Insulin recruits + stimulates transporters from the cytoplasm to move to the membrane.
What is the structure of the GLUT-4 protein?
Has a hydrophobic outer embedded to the membrane and a hydrophilic core, which allows glucose into the cell.
What are the effects of insulin on the liver?
- Increased protein synthesis.
- Decreased protolysis.
- Inhibits gluconeogenesis.
What are the effects of insulin on adipocytes?
- Breaks down fats in the blood so they can enter the adipocytes (lipoprotein lipase stimulated by insulin) into glycerol.
- Promotes formation of triglyceride and fat using glucose.
- Inhibits lipolysis.
What is a simple indicator of someone’s risk of ischaemic heart disease?
Their waist circumference - omental fat.
How is glycerol used by the liver?
- Make triglycerides (enters lipoprotein particles).
2. Gluconeogenesis (2 glycerols = glucose).
What fuel can the brain use and what cannot it use?
Can use glucose and ketone bodies. Cannot use fatty acids.
What is the effect of insulin on ketone bodies?
Insulin inhibits the conversion of fatty acyl CoA to ketone bodies. (glucagon does opposite)
What increases gluconeogenesis in the liver?
- Cortisol.
- Somatotrophin.
- Catecholamines.
- Glucagon.
What promotes the conversion of fatty acyl CoA to ketone bodies?
Glucagon.
What are ketone bodies?
Three water-soluble molecules produced by the liver from fatty acids during periods of low food intake:
- Acetone.
- Acetoacetic acid.
- Beta-hydroxybutyric acid.
What is the effect of insulin on glycogenolysis?
Insulin promotes the storage of glucose as glycogen (Glucose => Glucose-6-phosphate => glycogen).
What promotes glycogenolysis?
- Glucagon.
2. Catecholamines.
What is the effect of insulin on glucose uptake by muscle cells?
Promotes uptake of glucose via GLUT-4. Glucose is then stored as glycogen.
What inhibits uptake of glucose via GLUT-4 in muscle cells?
Stress hormones.
In a fasted state, what is your insulin:glucagon ratio and what does this result in?
Low insulin to glucose ratio.
Increase in protolysis, lipolysis, gluconeogenesis + glyconeolysis (HGO). Ketogenesis after prolonged time.
Decrease in AA concentration after a prolonged time.
In a fed state, what is your insulin:glucagon ratio and what does this result in?
High insulin to glucagon ratio.
Increase in protogenesis, lipogenesis and glycogen.
Decrease in protolysis, glucogenesis (stop HGO).
What happens during insulin induced hypoglycaemia?
Increase in insulin, glucagon, catecholamines, cortisol and somatotrophin.
Decrease in HGO and lipolysis.
What happens during T2DM?
Increase in LDL cholesterol, triglyceride and circulating NEFA.
Decrease in lipoprotein lipase activity, VLDL clearance and HDL cholesterol.
How do you distinguish between T1DM and T2DM?
T2DM has enough insulin to suppress ketone production and to stop protolysis. Therefore if glucose + ketone are high = T1DM.
What are the 2 pathways affected by insulin?
- Mitogenic pathway (MAPK).
2. Metabolic pathway (PI3K-Akt).
Which pathway has insulin resistance?
The metabolic pathway.
What types of tissue does insulin resistance reside in? (3)
- Liver tissue.
- Muscle tissue.
- Adipose tissue
What is compensatory hyperinsulinaemia?
Someone with insulin resistance making more insulin to maintain normal blood glucose.
How does high insulin harm a person?
Has an increased effect on the mitogenic pathway (MAPK).
How much the diet be controlled to manage T2DM?
Reduce fat, refined carbohydrates and sodium.
Increase complex carbohydrates and soluble fibre.
What are the features of someone with insulin resistance? (9)
- Hypertension.
- High triglyceride.
- Low HDL.
- High LDL.
- Fasting blood glucose > 6.0mmol/l.
- Adipocytokines.
- Inflammatory state.
- Energy expenditure affected.
- High Omental fat.
