Normal And Deregulated Metabolism

Question 1

3 metabolic states of the body

Answer 1

Absorptive
Post absorptive/fasting
Prolonged fasting/starvation

Question 2

What processes occur in the absorptive state

Answer 2

Glycogenesis
Lipogenesis
Glycolysis

Question 3

What processes occur in the post absorptive state

Answer 3

Glycogenolysis
Lipolysis
Gluconeogenesis

Question 4

Which tissue does not use glucose as fuel in the post absorptive state

Answer 4

Liver

Question 5

Why does the brain need constant glucose supply

Answer 5

Glucose is sole fuel for brain
Doesn’t store glucose

Question 6

How are free fatty acids used to generate acetyl CoA

Answer 6

Beta oxidation

Question 7

How are amino acids used in Gluconeogenesis

Answer 7

Enter TCA cycle

Question 8

Which process provides additional fuel during fasting

Answer 8

Ketogenesis

Question 9

Which cells keep using glucose during fasting

Answer 9

Brain
Red blood cells

Question 10

Where is glucose for brain and RBCs sourced during fasting

Answer 10

Hepatic and renal Gluconeogenesis

Question 11

What is the main source of energy during prolonged fasting

Answer 11

Ketone bodies

Question 12

When are ketone bodies synthesised

Answer 12

Prolonged fasting
Fasting
After prolonged exercise

Question 13

Which 2 intracellular electrolyte stores are especially depleted in Starvation

Answer 13

phosphate and potassium

Question 14

Re feeding syndrome

Answer 14

Hypophosphataemia, hypokalamia, and thiamine deficiency caused by already low serum levels due to starvation are further decreased due to transport of electrolytes into cells for synthesis of glycogen, triglycerides, and proteins

Question 15

What triggers re feeding syndrome

Answer 15

Insulin release after starvation

Question 16

What hormones inhibit and stimulate ketogenesis

Answer 16

Stim - glucagon
Inhibit - insulin

Question 17

What does the liver use as substrates for gluconeogenesis in the post absorptive state

Answer 17

Amino acids
Lactate
Glycerol

Question 18

What happens to excess CoA

Answer 18

Converted to ketone bodies by liver

Question 19

What fuel sources can the brain use

Answer 19

Glucose
Ketone bodies

Question 20

Diabetes mellitus

Answer 20

Insulin deficiency or resistance or both

Question 21

Type 1 diabetes

Answer 21

Disruption of insulin secreting cells causing very reduced or no insulin production

Question 22

Type 2 diabetes

Answer 22

Target cells have insulin resistance and insulin secreting cells cannot compensate

Question 23

Where are GLUT 4 receptors when blood glucose concentration is low

Answer 23

Inside cell

Question 24

How does insulin work when blood glucose is high

Answer 24

Binds to receptor -> autophosphosphorylation of receptor on tyrosine -> IRS can bind to receptor ->IRS phosphorylated on tyrosine -> binds to PI3K -> PI3K moves from cytoplasm -> GLUT 4 transporters insert on membrane

Question 25

What needs to happen to IRS for PI3K to bind

Answer 25

IRS must be phosphorylated on tyrosine

Question 26

What can cause insulin resistance

Answer 26

Decreased insulin receptor numbers Decreased catalytic activity of receptor Incr activity of tyrosine phosphatases Decr GLUT 4 levels and function Incr IRS receptor phosphorylation Decr PI3K/Akt activity

Question 27

How can pro inflammatory cytokines, saturated FFAs, and amino acids cause insulin resistance

Answer 27

Phosphorylate IRS incr IRS degradation

Question 28

What happens when insulin acts on resistant cells

Answer 28

Messaging cascade stopped before reaching GLUT 4

Question 29

What causes the signalling process caused by insulin binding to be halted in insulin resistant cells

Answer 29

IRS already phosphorylated so can’t be phosphorylated by receptor

Question 30

Hyperglucagonaemia

Answer 30

Excessive circulating glucagon levels

Question 31

What is islet compensation

Answer 31

Increase in beta cell size, number, and function in response to insulin resistance

Question 32

Why does islet compensation occur in response to insulin resistance

Answer 32

Glucose tolerance can be maintained by increased insulin secretion

Question 33

Do alpha or beta cells in islets of langerhans increase in diabetes

Answer 33

Beta

Question 34

What can cause hypoglycaemia in patients without diabetes

Answer 34

Critical illness Counter regulatory hormone deficiencies Insulin overproduction

Question 35

Symptoms of hypoglycaemia

Answer 35

Trembling Palpitations Sweating anxiety Hunger Tingling Confusion Difficulty concentrating Weakness Vision changes Dizziness Tiredness Seizures Loss of consciousness Coma

Question 36

Causes of hypoglycaemia in diabetics

Answer 36

Overuse of insulin Skipping meals Incr physical activity Alcohol excess

Question 37

How does alcohol cause hypoglycaemia in diabetics

Answer 37

Inhibition of gluconeogenesis

Question 38

What can recurrent hypoglycaemia lead to

Answer 38

Suppression of normal physiological counter regulatory response Impaired awareness of hypoglycaemia

Question 39

What impairs awareness of hypoglycaemia

Answer 39

Whole body adaptations to repeated insulin induced hypoglycaemia and impaired counter regulatory response

Question 40

How can the liver cause hyperglycaemia

Answer 40

Decr glycogen synthesis Impaired lipogenesis Incr Gluconeogenesis Incr glycogenolysis

Question 41

How can muscles increase hyperglycaemia

Answer 41

Decr glucose uptake Decr glycogen synthesis Incr protein catabolism

Question 42

How can adipose increase hyperglycaemia

Answer 42

Decr glucose uptake Decr lipogenesis Incr lipolysis

Question 43

How can the polyol pathway cause cell damage

Answer 43

Oxidative stress ROS production AGE production

Question 44

How does the polypol pathway affect blood vessels

Answer 44

Oxidase damage to macromolecules, impaired NO signalling, and pro inflammatory signalling increases vasoconstriction and impairs vasodilation

Question 45

What pathways is excess glucose diverted to in hyperglycaemia

Answer 45

Polyol pathway PKC pathway AGE pathway

Question 46

What does the PKC pathway cause

Answer 46

Incr vascular permeability and occlusion Incr ROS Inflammation Mitochondrial dysfucntion

Question 47

What does AGE stand for

Answer 47

Advanced glycation end products

Question 48

How does the AGE pathway damage cells

Answer 48

Production of AGE - cause Protein Structure modifications Gene expression Pro inflam molecule secretion Free radical production