introduction to diabetes Flashcards
1
Q
- In which cell types are GLUT-4 transporter proteins most commonly found?
- Do GLUT-4 transporter proteins respond to insulin?
A
Common in myocytes and adipocytes
Yes
2
Q
- How does insulin affect proteolysis and protein synthesis respectively in myocytes?
A
Inhibits proteolysis as protein is not needed as a fuel source
Stimulates protein synthesis to use the proteins for storage
3
Q
- What effect does GH and IGF-1 have on protein synthesis in myocytes?
- What effect does cortisol have on proteolysis in myoctes?
- What is a gluconeogenic amino acid?
A
Stimulates it
Stimulates it An amino acid that can be converted into glucose through gluconeogenesis
4
Q
- What hormone leads to an increase in uptake of gluconeogenic amino acids in the liver?
- What role does glucagon have in the liver?
A
Glucagon
Stimulates proteolysis to produce more gluconegenic amino acids These amino acids are then converted into glucose in gluconeogenesis which is also stimulated by glucagon (as well as cortisol)
5
Q
- What effect does insulin have on the hepatic glucose output in the fed state?
A
It reduces hepatic glucose output
Because it inhibits gluconeogensis So less glucose is synthesised
6
Q
- What does Lipoprotein Lipase break Triglycerides down into to be absorbed into adipocytes and what hormone is this process stimulated by?
A
Glycerol and Non-Esterified Fatty Acids (NEFA)
Insulin
7
Q
- What does Insulin do in the adipocytes?
A
Increases uptake of glucose via GLUT-4
Converts Glycerol and NEFA into triglycerides again for later use when needed - lipogenesis Also uses glucose as a substrate for the re-synthesis of triglyceride (due to glycolysis, acetyl Co A produced, converted into fatty acids), instead of NEFA to reduce glucose levels Thereby inhibiting the breakdown of triglycerides in the adipocytes back into NEFA and Glycerol
8
Q
- What effects does GH and Cortisol have on the triglycerides in the adipocytes in the fasting state?
- In the fasting state what happens to the glycerol taken up by the liver?
A
Stimulates breakdown of triglycerides into Glycerol and NEFA to be used as an alternative energy source once transported into the liver - stimulates lipolysis
It is converted into glucose in process, gluconeogenesis Increasing hepatic glucose output
9
Q
- In the fed state what happens to the glycerol taken up by the liver?
- Can the brain utilise NEFA as a fuel?
- What can the brain use as a fuel?
A
Converted into triglycerides
no
Glucose, Ketone Bodies
10
Q
- In the fed state, what does insulin do once NEFA is uptaken by the liver?
A
NEFA converted into fatty Acyl-CoA
Insulin inhibits the conversion of Fatty Acyl-CoA into ketone bodies This prevents it from being used as an alternative metabolic substrate to glucose The opposite happens in the fasting state where ketone bodies are produced
11
Q
- What does it mean if there is a high level of ketones and glucose?
- In the fed state what happens to glucose in the liver?
A
There is an issue with insulin secretion#
It is converted into Glucose-6-P This is then converted into Glycogen (stimulated by insulin)
12
Q
- In the fasting state what happens to glycogen in the liver?
- In the fed state what happens to Glucose in myocytes?
A
It is broken down (process stimulated by glucagon) - Glycogenolysis
It is converted into glycogen to be stored and used when the myocyte needs energy It is also used in aerobic respiration
13
Q
- What effect does Glucagon and GH have on the GLUT-4 transporters in myocytes?
- In the fasting state why is amino acid concentration increased initially and then decreased when prolonged?
A
Inhibits uptake of glucose via GLUT-4 to allow more glucose to remain in circulation and increase the blood glucose levels
Increased due to increased proteolysis and then decreased due to more gluconeogenesis to increase hepatic glucose output
14
Q
- What tests can be carried out to make a diagnosis of diabetes?
A
Fasting glucose > 7.0mmol/L
Random glucose > 11.1mmol/L Oral glucose tolerance test HbA1c (>48mmol/L)
15
Q
- How many tests do you need to diagnose diabetes?
A
2 positive tests
Or 1 positive test and symptoms
16
Q
- Desribe the pathophysiology of Type 1 Diabetes Mellitus (T1DM)
A
Autoimmune condition that eventually leads to a T-Cell mediated destruction of the insulin-producing beta cells in the pancreas, leading to absolute insulin deficiency
17
Q
- How does T1DM lead to osmotic diuresis?
A
Increased glucose in blood so more glucose in urine
Lowering water potential of the urine, so water enters urine via osmosis, leading to a lot of water loss
18
Q
- How does diabetic ketoacidosis occur?
A
Less insulin is there to down-regulate the breakdown of triglycerides in adipocytes
So more triglycerides are broken down into NEFA and Glycerol NEFA are then converted into ketone bodies in the liver (which would also normally be inhibited by insulin), leading to a build up of ketones
19
Q
- What do patients with T1DM usually present with?
A
Weight loss
Hyperglycaemia Glycosuria → polyuria, nocturia, polydipsia Ketones in blood and urine
20
Q
- What are some diagnostic tests for T1DM over T2DM?
A
Antibodies: GAD (glutamic acid decarboxylase) , IA2 (islet antibody 2)
C-Peptide (usually not present- signifies insulin production is low) Presence of ketone bodies
21
Q
- Which hormones induce a counterregulatory response to hypoglycaemia?
A
Glucagon
Catecholamines Cortisol Growth Hormone
22
Q
- What is the counterregulatory response to hypoglycaemia?
A
Increased HGO with glycogenolysis and gluconeogenesis
Increased lipolysis
23
Q
- What are some of the autonomic signs and symptoms of hypoglycaemia?
A
Sweating
Pallor Palpitations Shaking
24
Q
- What are some of the neuroglycopenic syptoms of hypoglycaemia?
A
Slurred speech
Poor vision Confusion Seizures Loss of consciousness
25
- What is severe hypoglycaemia?
An episode where a person needs third party assistance for treatment
26
- What effect does insulin resistance have on Triglyceride and HDL concentration in the plasma ?
High Triglyceride concentration in plasma as insulin function is lacking and so LPL cannot breakdown TG into Glycerol and NEFA
Low HDL concentration - overproduction of VLDL leading to increased TG plasma levels which results in lower levels of HDL
27
- How do T2DM patients usually present?
Hyperglycaemia
Overweight
Dyslipidaemia
Less osmotic symptoms
Insulin resistance
Later insulin deficiency
28
- What are some of the risk factors of T2DM?
Age
High BMI
Ethnicity
Family Hx
Inactivity
29
- What dietary reccomendations could be given to a patient with T2DM?
Reduce calories as fat or refined carbohydrate
Increase calories as complex carbohydrate
Increase soluble fibre
Decrease sodium
Total calories control
30
- What management strategies can be made for patients with T1DM?
```
Exogenous insulin (basal-bolus regime) - 1 long acting insulin injection once or twice a day and then quick injections just before meals
- plan meals, try to match insulin dose with meal, eat after a short interval
```
Self-monitoring of glucose - fingerprick testing
Structured education
Technology
31
- What management strategies can be made for patients with T2DM?
Diet
Oral medication
Structured education
May need insulin later - if loss of beta cell function later on in life
32
- What are some of the long-term diabetes complications that can be avoided through certain management strategies?
Retinopathy
Neuropathy
Nephropathy
Cardiovascular
33
Describe how insulin stimulates the uptake of glucose
insulin binds to insulin receptor
insulin turns on the movement of Glut 4 (charter proteins) into the plasma membrane
glucose moves into cell via glut 4
34
List all the effects of insulin
```
increase glycogenesis
decrease gluconeogenesis
inc protein synthesis
decrease proteolysis
decrease ketogenesis
inc lipogenesis
stops hepatic glucose output
```
35
what happens when insulin falls due to starvation
```
hepatic glucose output increases
as hepatic glycogen releases glucose
low insulin levels switch on lipolysis
NEFA released
low insulin so NEFA converted in liver to ketones
ketones used as fuel source for brain
```
36
How does diabetic ketoacidosis occur
what are the blood tests results of this
No insulin- so ketone production is not inhibited
so too many ketones made so blood is slightly acidic
ph less than 7.5
ketones +3
HC03- under 15
37
what happens when insulin is injected with no food being eaten
insulin binds to receptor
blood sugar goes even lower as glucose is uptaken, so no glucose fuel for brain
insulin prevents production of ketone bodes- so no ketones for brain fuel either
results in confusion and unconsciousness
38
which tissues does insulin resistance occur in
what happens when you have insulin resistance
liver, muscle, adipose tissue
insulin rises after a meal, however not all of the GLUT 4 transporters go to plasma membrane
so not all of the glucose up taken into cell- hyperglycaemia
so body keeps producing more insulin - hyperinsulinemia
no ketones as insulin suppresses ketogenesis#
it also suppresses proteolysis
