6 An Introduction To Diabetes Mellitus Flashcards
(41 cards)
Q: How does insulin affect glucose? (2)
A: Decrease hepatic glucose output
Increase uptake of glucose by muscles
Q: How does insulin affect protein?
A: Decreased proteolysis
Q: How does insulin affect lipids? ketones? Reason?
A: Decrease lipolysis
Decrease ketogenesis
once we’ve eaten there is no need to make ketones/lipids
Q: What are the 3 molecules that insulin affects (metabolic effects)?
A: glucose
protein
lipid
Q: Describe glucose uptake through GLUT4. Where is it particularly abundant? (2) What stimulates it? What is its structure? How much does it increase glucose uptake?
A: Glucose is mainly taken up by Glucose Transporter 4 (GLUT-4)
GLUT-4 is particularly abundant in muscle and adipose tissue
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 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
Q: Which cells don’t have insulin sensitive glucose transporters? (2) What variations exist?
A: brain since glucose must get into brain cells regardless or RBC
pancreas has GLUT2 (beta cells)
Q: Using a muscle cell as an example, show how insulin affects protein. Include other hormones.
A: \_\_\_\_\_\_\_\_\_\_\_\_\_
| |
| protein |
| | / \ |
| \ / | | O2 in
protein -> aa (proteolysis)
(- insulin) (+ cortisol)
Insulin stops proteolysis
Cortisol increases proteolysis when we’re stressed
aa -> protein (protein synthesis)
(+ insulin) (+ IGF 1 : growth hormone)
aa out are gluconeogenic eg alanine = go to liver to make glucose (fuel source)
Amino acids could be oxidised in the muscle cell
(- insulin)
Q: Where does most glucose present in our blood come from?
A: made by us
Q: What is a short term energy store? Long term?
A: glycogen (keep us going 6-8hrs between meals)
fat
Q: What should glucose concentration be in blood?
A: 4-7mmol/L
Q: Explain gluconeogenesis in liver cells including the effect of insulin and other hormones (diagram).
A: liver cell
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 where aa becomes protein (stimulated by insulin)
proteolysis in opposite direction can occur (stimulated by protein defic and glcg)
The amino acids can be used to make glucose - GLUCONEOGENESIS (insulin inhibits gluconeogenesis while Somatotrophin, Cortisol, Catecholamines and Glucagon increase gluconeogenesis)
The glucose produced from gluconeogenesis can then enter the circulation as HEPATIC GLUCOSE OUTPUT (HGO)- helps maintain sugar levels
Q: Recall the fuel stores in a normal man.
STORE: CHO (liver + muscle), protein, fat
WEIGHT (Kg), ENERGY (KJ/g), TIME
A: CHO= 0.5, 16, 16 hrs
protein= 8-9, 17, 15 days
fat= 9-10, 37, 30-40 days
Q: Explain how insulin and other hormones affect adipocytes.
A: 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 (GLUT4 which is stimulated by insulin) and can be used to make NEFA
Glucose can also be chopped up to make two glycerols and the fatty acids can be stuck to the glycerol to make triglycerides (insulin promotes)
TGs can be broken back down
- production of glycerol is reduced by insulin
- production of NEFA is encouraged by cortisol, GH, Catecholamines (fight/flight) -> released back into circulation
Q: What is lipoprotein lipase?
A: hormone sensitive lipase particular to capillary beds
Q: What are the 2 effects insulin has on fat depending on where it acts?
A: Blood - breaks down the fats so that it can enter the adipocyte
Adipocyte - promotes formation of triglyceride and storage of fat and inhibits lipolysis
Q: Draw a simple diagram for circulation and explain.
A: lungs // heart // liver // gut // all tissues
Blood reaches the gut and there is a portal system connecting the intestines to the liver (has its own circulation)
The blood passes through the liver for the absorbed food to be processed
Q: What is a simple indicator of an individual’s risk of ischaemic heart disease?
A: omental fat/waist circumference
Q: Explain the use of glycerol by the liver?
A: Glycerol coming from adipocytes and food enters the liver (particularly come from omental circulation since omental adipocytes have a more profound effect metabolism than adipocytes in arm/leg)
then : glycerol -> glycerol 3 phosphate -> triglycerides
Glycerol could also be used to make glucose - form of gluconeogenesis (Two glycerols can be stuck together)= supports HEPATIC GLUCOSE OUTPUT
Q: After a fast of 10 hours, what percentage of our hepatic glucose output is supported by new glucose production?
A: 25
Q: Where can the brain get energy? Where can it not get it from?
A: Brain CAN use: Glucose + Ketone Bodies
Brain CAN NOT use: Fatty Acids (no ability to do lipolysis since no enzymes present to facilitate)
Q: How does insulin and other hormones affect ketone body synthesis in the liver?
A: Fatty acids (some generated from lipolysis) can enter the liver and be used to make ketone bodies
NEFA -> FA acyl CoA
FA acyl CoA -> acetyl CoA -> acetoacetate -> acetone + 3 OH-B
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
Q: When should there be high ketone bodies present and when should there not be? Why is this clinically useful?
A: If someone has high insulin then they should stop making ketone bodies
High Blood Glucose + High Ketone Bodies = INSULIN DEFICIENT (abnormal)
testing sugars and ketones is useful when determining a person does not have enough insulin
Q: Explain the effect of insulin and other hormones on hepatic glycogenolysis (in liver).
A: glycogenolysis- no new synthesis, just liberating
Glucose enters the liver and is converted to Glucose-6-Phosphate
G6P -> stored glycogen (Insulin promotes)
glycogen -> G6P (glucagon and Catecholamines promote)
G6P can be converted back into glucose to support HGO
Q: Name 2 processes that support hepatic glucose output.
A: Gluconeogenesis
Glycogenolysis
