MOOC 3 Pathophysiology of Cardiometabolic Disease
18 important questions on MOOC 3 Pathophysiology of Cardiometabolic Disease
What are the four major types of diabetes?
- Diabetes type 1
- occurs often in general young thin people who develop diabetes at an early age
- Diabetes type 2 (90% of the time)
- is typically present in the obese, middle-aged individual with family members who also suffer from diabetes
- Gestational diabetes
- the presence of diabetes during pregnancy, which disappears after delivery
- however, these women are at increased risk to develop diabetes again in later life
- Rare types of diabetes
- ranting from purely genetic disorder to diabetes associated with other diseases
- such as diseases of the pancreas,
- or diabetes induced by drugs or toxins
The major organs involved in the regulation of your blood glucose are .. (5)
skeletal muscle
fat- or adipose- tissue
intestine
pancreas
What will happen after ingesting a meal and the glucose enters the blood?
- The rise in glucose will trigger the Beta-cells of the pancreas
- to secrete the hormone insulin
- insulin will stimulate the uptake of glucose in skeletal muscle and liver and adipose tissue
- At the same time, insulin suppresses glucose output from the liver
This all together controls the increase in blood glucose levels.
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After a while, when all nutrients from the meal are digested, the blood glucose level will decrease. What is done to prevent a too low blood glucose level?
- After a meal the insulin levels go down
- the liver starts to release glucose again
- while glucose uptake in insulin sensitive tissues will be reduced
- this all together prevents hypoglycaemia, or a too low blood glucose level.
- and provides glucose to tissues who heavily rely on glucose as an energy source, like the brain
What are the two key features in the pathogenesis of diabetes?
- the development of insulin resistance
- is when cells don't respons well to insulin
- as a result, they can't easily take up glucose from your blood
Beta-cell function
- the capacity of the B-cell to secrete insulin
- in the case of diabetes --> Beta-cell failure
What are the two major locations of adipose tissue?
Visceral adipose tissue
Visceral adipose tissue is more 'active' than subcutaneous adipose tissue. What thus this mean?
- For example that the rate and controle of breakdown of lipids and the release of fatty acids is much higher.
- and the visceral adipose tissue has also a more direct connection to the liver
What is ectopic fat deposition and where can you find it?
- but it is lipids located in small droplets within the cells.
The liver, skeletal muscle and heart are able to store small quantities of lipid, which can be used to create energy.
However, when storage of these lipids exceeds the capacity of the cell to use these lipids, it can interfere with normal function of the cell ---> lipotoxicity
Insulin has much more metabolic actions than the uptake of glucose, namely
+ Glycogen synthesis
+ Lipid formation
+ Protein synthesis
- Gluconeogenesis
- Breackdown glycogen
- Lipolysis
- Protein breakdown
The pancreas is a gland located in the upper part of your abdomen. It has a dual role.
- It secretes enzymes to break down proteins, lipids, and carbohydrates in food
- It produces and secretes hormones such as insulin and glucagon into the bloodstream
- produced by the islets of Langerhans
- covers 5% of the pancreas
The islets of Langerhans contain two type of cells. Name them and what do they do
- glucagon
- low blood glucose levels
- release of glucose
Beta cells
- insulin
- high blood glucose levels
- uptake & storage of glucose
How is insulin released from the Beta-cells?
- Inside the beta cell insulin is produced and stored in small vesicles
- glucose ^ --> glucose uptake in the Beta cells, which triggers a series of actions
- ultimately results in the influx of calcium into the cell, which triggers the release of insulin.
What other nutrients can increase glucose-induced insulin secretion?
- Free fatty acids
- Amino acids
- Incretins
- are hormones secreted y intestinal cells after ingestion of a meal
There are more factors, beside lipotoxity, that can compromise beta-cell function, namely
- Inflammation and oxidative stress
- Deposition of a peptide called amyloid in the beta cells
- Hyperglycaemia
3 methods to measure insulin resistance
- Simple index - fasting blood
- Oral Glucose Tolerance Test
- Clinical research test: "Clamp"
Researchers have proposed several formulas that can estimate the level of insulin resistance, based on glucose and insulin levels in your blood. We call this ....
as they do not directly measure insulin resistance, but estimate it.
What is the most frequently used index? And who do you calculate it
HOMA = [insulin] x [glucose] / 22.5
- value < 1
- indicates that you insulin action is better than normal: you are more insulin sensitive
- Value >1
- indicates some insulin resistance, with the higher the value, the more insulin resistant you are.
Benefits:
- quick
- easy
- cheap
- large populations
Disadvantage
- it is an estimation, it is not a direct quantification of insulin action
The well-known OGTT, the oral glucose tolerance test, (which is also used to diagnose diabetes)
OGTT is also not a direct quantification of insulin action
benefits
- easy
- more information
disadvantage
- more time
- more work for researcher
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