Introduction to Diabetes Mellitus Flashcards
What effects does insulin have on glucose?
Decrease hepatic glucose output. Increase uptake of glucose by muscles.
Describe insulins effects on protein metabolism
Decreased proteolysis
How does insulin effect lipid metabolism
Decrease lipolysis Decrease ketogenesis Ketone bodies are an energy source instead of glucose when we have not eaten. The brain can even use glucose. If we eat a meal there is no need to make ketones. If someone has ketones in their urine, they are difficient insulin. After we had a meal there is no need to make ketones.
List the other effects (mitagenic) of insulin
Lipoproteins Smooth muscle hypertrophy especially in arteries. Ovarian Function Clotting
In what tissues is GLUT 4 very abundant in?
GLUT-4 is particularly abundant in muscle and adipose tissue. NOT LIVER
What stimulates GLUT 4 to move from vesicle to the plasma membrane?
Insulin GLUT-4 is insulin responsive
What is the structure of a GLUT-4 receptor.
It has hydrophobic elements on the outside embedded in the membrane and a hydrophilic core which allows glucose into the cell - it is insulin responsive .
GLUT-4 sits in vesicles within the cytoplasm - insulin recruits them to the membrane thus causing up to 7-fold increase in glucose uptake.
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By how much does GLUT-4 increase glucose uptake?
7x
List all of the effects of insulin on protiein?
This is a muscle cell .
Insulin stops proteolysis.
Cortisol increases proteolysis when we’re stressed.
Amino acids could be oxidised in the muscle cell and insulin prevents oxidation of amino acids.
Insulin increases the re-synthesis of proteins from amino acids -Protein synthesis.
The amino acids could get in to the circulation and move to the liver where it can be used to produce glucose- these are the gluconeogenic amino acids. add pic
Name something that stimulates protein synthesis in the liver?
Insulin
List the effects of insulin on the liver
This is the LIVER.
Gluconeogenic amino acids enter the liver via specific transporter channels.
Glucagon increases the uptake of amino acids by the liver.
In the liver, protein synthesis is stimulated by insulin.
The amino acids can, however, be used to make glucose - GLUCONEOGENESIS.
Insulin inhibits gluconeogenesis.
Somatotrophin, Cortisol, Catecholamines and Glucagon increase gluconeogenesis.
The glucose produced from gluconeogenesis can then enter the circulation as HEPATIC GLUCOSE OUTPUT (HGO).
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So insulin has TWO effects on fat depending on where it acts: List these effects.
Blood - breaks down the fats so that it can enter the adipocyte Adipocyte - promotes formation of triglyceride and storage of fat and inhibits lipolysis
List the effects of Insulin on Adipocytes
Here we have an adipocyte and a blood vessel next to it .
Triglycerides come in the vasculature and are too big to enter the adipocyte directly .
Triglycerides have to be broken down by LIPOPROTEIN LIPASE before it can enter the adipocyte.
Lipoprotein Lipase is stimulated by insulin.
Triglyceride is broken down into glycerol and non-esterified fatty acids which are absorbed into the adipocyte.
Glucose also enters the adipocyte and can be used to make NEFA -non-esterified fatty acids.
Glucose can also be chopped up to make two glycerols and the fatty acids can be stuck to the glycerol to make triglycerides .
Insulin will stop lipolysis and the four counter-regulatory hormones will promote lipolysis.
So insulin has TWO effects on fat depending on where it acts:
Blood - breaks down the fats so that it can enter the adipocyte
Adipocyte - promotes formation of triglyceride and storage of fat and inhibits lipolysis. add pic
What is a simple indicator of ischeamic heart disease?
So, omental fat/waist circumference is a simple indicator of an individual’s risk of ischaemic heart disease
Where does glycerol from food and adipocytes enter to?
Liver
What is glycerol used to make in the liver?
Triglycerides or glucose. Glycerol could also be used to make glucose - form of gluconeogenesis . Two glycerols can, in effect, be stuck together to make glucose - this supports HEPATIC GLUCOSE OUTPUT.
After a fast of 10 hours, what percentage of our hepatic glucose output is supported by new glucose production.
After a fast of 10 hours, 25% of our hepatic glucose output is supported by new glucose production
Describe the diagram below of the use of glycerol by the liver. add pic.
Glycerol coming from adipocytes and food enters the liver.
This glycerol is used to make Triglycerides.
The triglycerides can then enter lipoprotein particles.
Glycerol could also be used to make glucose - form of gluconeogenesis .
Two glycerols can, in effect, be stuck together to make glucose - this supports HEPATIC GLUCOSE OUTPUT.
Glycerol can be used to make glucose but fat CANNOT re-enter the glucose pathway.
After a fast of 10 hours, 25% of our hepatic glucose output is supported by new glucose production.
List the fuels the brain can use?
Glucose Ketone Bodies BRAIN CANNOT USE FATTY ACIDS- it wouldnt be a good idea for brain tissue to break down fat.
How does insulin effect Ketone Body Synthesis in the Liver
Fatty acids generated from lipolysis can enter the liver and be used to make ketone bodies.
Insulin INHIBITS the conversion of Fatty Acyl CoA to Ketone Bodies .
Glucagon PROMOTES the conversion of Fatty Acyl CoA to Ketone Bodies.
Ketone bodies will enter the circulation and mainly be used by the muscles.
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State the relationship between high insulin and ketone body manufacturing.
If someone has high insulin then they should stop making ketone bodies.
What do you have if you have high ketone bodies and high blood glucose
High Blood Glucose + High Ketone Bodies = INSULIN DEFICIENT Measure ketones in blood and urine.
Ketone Bodies = three water-soluble molecules that are produced by the liver from fatty acids during periods of low food intake or carbohydrate restriction. Name these 3 molecules.
ACETONE. ACETOACETIC ACID. BETA-HYDROXYBUTYRIC ACID.
What do you have high levels of when you are fasting?
Ketone bodies
What are the two processes that support hepatic glucose output?
Gluconeogenesis Glycogenolysis
State the effects of insulin on glycogenolysis?
INSULIN INHIBITS GLYCONGENOLYSIS
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Glucagon and Catecholamines promotes ……….. in the liver.
Glucagon and Catecholamines promotes GLYCOGENOLYSIS in the liver. add pic
How do stress hormones effect the uptake of glucose by GLUT-4?
Stress hormones tend to INHIBIT uptake of glucose by GLUT-4
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Muscle cells cannot release glucose.
Name the substance that increase in amount when fasting and name the substances that decrease in amount whilst fasting.
INCREASE IN: Concentration of NEFA. Proteolysis. Lipolysis. Hepatic Glucose Output (from glycogenolysis and gluconeogensis). DECREASE IN: Amino Acid Concentration (when prolonged).
Name the substance that increase in amount when fed and name the substances that decrease in amount whilst fasting.
INCREASE IN: Glycogen Protein Synthesis Lipogenesis DECREASE IN: Gluconeogenesis Proteolysis
What is the state of the body when fasting? Talk about the amount the of fatty acids, the insulin the glucagon ratio and the amino acid conc. Also talk about what substrate the brain and muscle will use.
Low insulin to glucagon ratio. Increase in NEFA Decrease in amino acids when prolonged Muscle to use lipid Brain to use glucose, later ketones
What is the state of the body when fed? Talk about the insulin to glucagon ratio, Hepatic glucose output, gluconeogenesis, protein synthesis, proteolysis and lipogenesis.
High insulin to glucagon ratio Stop HGO Increase protein synthesis and stop porteolysis increase lipogenesis
Explain the graph below add pic
The 21 yr old lady has type 1 diabetes. When she was given the insulin and the glucose her blood sugar level didn’t rise that much. She was insulin difficient. The 60yr old lady has type 2 diabetes. She is insulin insensitive. Insulin did not work that well, she is also insulin resistant.
What is the presentation of type 1 diabetes?
Proteolysis with weight loss.
Hyperglycaemia. Glycosuria with osmotic symptoms (polyuria and polydipsia).
Ketonuria.
Absolute Insulin dificiency.
Polydipsia.-Thirst
Polyphagia- excessive eating
Polyuria- large amounts of urine
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What condition is almost inevitable for type 1 diabetes?
Hypoglyceamia
Why do some patients with diabetes have insulin induced hypoglyceamia?
- Too much insulin injected. - Nearly impossible to have the write amount og glucose -There is usally a store of insulin learking subcutaneously, this insulin can leak into the blood stream.
How does the body respond to an insulin induced hypoglyceamia?
In this state you have high insulin but low glucose. Increase in glucagon Increase in Catecholamines Increase in Cortisol Increase in Growth Hormone Increase in HGO later with glycogenolysis and Gluconeogenesis- when the high insulin has broken down Increase in Lypolysis
How would you treat hypglyceamia.
Sugary drink Glucagon injection in the muscle
Where does insulin resistance reside in. What tissues and organs.
Insulin resistance resides in the LIVER, MUSCLE and ADIPOSE TISSUE .
For insulin resistant individuals, what is there enough insulin to do that patients with type 2 diabetes can’t do, but patients with type 1 diabetes can do?
Ketogenesis Proteolysis
How would you tell if a patient has type 1 or type 2 diabetes.
In T2DM there is enough insulin to suppress ketone production - and they usually have enough insulin to stop break down of protein. So, this allows you to differentiate between T1DM and T2DM quite crudely - if someone is losing weight and has other diabetes-like symptoms then they are most likely to have T1DM. If their Glucose AND Ketones are high then they are likely to have T1DM.
What is there an increase in when you have uncontrolled type 2 diabetes?
Circulating NEFA Triglyceride LDL Cholesterol
What is there a decrease in when you have uncontrolled type 2 diabetes?
Lipoprotein lipase activity VLDL clearance (due to reduced lipoprotein lipase activity) HDL Cholesterol
Name 7 common presentation of a pateint with type 2 diabetes?
-Insulin resistance -60-80% obese - Large waist circumference -Dyslipidaemia- High triglycerides and low HDL -Later insulin deficiency -Hyperglycaemia- higher fasting glucose amount -Less osmotic symptoms -With complications
Name the two pathways effected by insulin
-Mitogenic Pathway (MAPK) -Metabolic Pathway (PI3K-Akt)
What pathway involves MAPK
-Mitogenic Pathway (Growth and proliferation)
What pathway involves PI3K-Akt
Metabolic Pathway
Someone with insulin resistance will have a compensatory hyperinsulinaemia so they make enough insulin to maintain a normal blood glucose. This will happen in someone developing T2DM before the blood glucose is elevated. Why is this bad?
HIGH INSULIN is still harming them because it has an increased effect on the mitogenic pathway (MAPK). INsulin resistance does not effect the MAPK This cause smooth muscle hypertrophy ( high blood pressure) Effect ovarian function Effect Clotting Effect lipoprotien This is why type 2 diabetes have hypertension and dislipideamia. High LDL conc and low HDL conc.
How should a patient with diabetes control their diet?
Total calories control reduce calories as fat reduce calories as refined carbohydrate increase calories as complex carbohydrate increase soluble fibre- which prolongs exposure to glucose Decrease sodium- becuase of hypertension
