Normal And Deregulated Metabolism Flashcards
3 metabolic states of the body
Absorptive
Post absorptive/fasting
Prolonged fasting/starvation
What processes occur in the absorptive state
Glycogenesis
Lipogenesis
Glycolysis
What processes occur in the post absorptive state
Glycogenolysis
Lipolysis
Gluconeogenesis
Which tissue does not use glucose as fuel in the post absorptive state
Liver
Why does the brain need constant glucose supply
Glucose is sole fuel for brain
Doesn’t store glucose
How are free fatty acids used to generate acetyl CoA
Beta oxidation
How are amino acids used in Gluconeogenesis
Enter TCA cycle
Which process provides additional fuel during fasting
Ketogenesis
Which cells keep using glucose during fasting
Brain
Red blood cells
Where is glucose for brain and RBCs sourced during fasting
Hepatic and renal Gluconeogenesis
What is the main source of energy during prolonged fasting
Ketone bodies
When are ketone bodies synthesised
Prolonged fasting
Fasting
After prolonged exercise
Which 2 intracellular electrolyte stores are especially depleted in Starvation
phosphate and potassium
Re feeding syndrome
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
What triggers re feeding syndrome
Insulin release after starvation
What hormones inhibit and stimulate ketogenesis
Stim - glucagon
Inhibit - insulin
What does the liver use as substrates for gluconeogenesis in the post absorptive state
Amino acids
Lactate
Glycerol
What happens to excess CoA
Converted to ketone bodies by liver
What fuel sources can the brain use
Glucose
Ketone bodies
Diabetes mellitus
Insulin deficiency or resistance or both
Type 1 diabetes
Disruption of insulin secreting cells causing very reduced or no insulin production
Type 2 diabetes
Target cells have insulin resistance and insulin secreting cells cannot compensate
Where are GLUT 4 receptors when blood glucose concentration is low
Inside cell
How does insulin work when blood glucose is high
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
What needs to happen to IRS for PI3K to bind
IRS must be phosphorylated on tyrosine
What can cause insulin resistance
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
How can pro inflammatory cytokines, saturated FFAs, and amino acids cause insulin resistance
Phosphorylate IRS
incr IRS degradation
What happens when insulin acts on resistant cells
Messaging cascade stopped before reaching GLUT 4
What causes the signalling process caused by insulin binding to be halted in insulin resistant cells
IRS already phosphorylated so can’t be phosphorylated by receptor
Hyperglucagonaemia
Excessive circulating glucagon levels
What is islet compensation
Increase in beta cell size, number, and function in response to insulin resistance
Why does islet compensation occur in response to insulin resistance
Glucose tolerance can be maintained by increased insulin secretion
Do alpha or beta cells in islets of langerhans increase in diabetes
Beta
What can cause hypoglycaemia in patients without diabetes
Critical illness
Counter regulatory hormone deficiencies
Insulin overproduction
Symptoms of hypoglycaemia
Trembling
Palpitations
Sweating
anxiety
Hunger
Tingling
Confusion
Difficulty concentrating
Weakness
Vision changes
Dizziness
Tiredness
Seizures
Loss of consciousness
Coma
Causes of hypoglycaemia in diabetics
Overuse of insulin
Skipping meals
Incr physical activity
Alcohol excess
How does alcohol cause hypoglycaemia in diabetics
Inhibition of gluconeogenesis
What can recurrent hypoglycaemia lead to
Suppression of normal physiological counter regulatory response
Impaired awareness of hypoglycaemia
What impairs awareness of hypoglycaemia
Whole body adaptations to repeated insulin induced hypoglycaemia and impaired counter regulatory response
How can the liver cause hyperglycaemia
Decr glycogen synthesis
Impaired lipogenesis
Incr Gluconeogenesis
Incr glycogenolysis
How can muscles increase hyperglycaemia
Decr glucose uptake
Decr glycogen synthesis
Incr protein catabolism
How can adipose increase hyperglycaemia
Decr glucose uptake
Decr lipogenesis
Incr lipolysis
How can the polyol pathway cause cell damage
Oxidative stress
ROS production
AGE production
How does the polypol pathway affect blood vessels
Oxidase damage to macromolecules, impaired NO signalling, and pro inflammatory signalling increases vasoconstriction and impairs vasodilation
What pathways is excess glucose diverted to in hyperglycaemia
Polyol pathway
PKC pathway
AGE pathway
What does the PKC pathway cause
Incr vascular permeability and occlusion
Incr ROS
Inflammation
Mitochondrial dysfucntion
What does AGE stand for
Advanced glycation end products
How does the AGE pathway damage cells
Production of AGE - cause
Protein Structure modifications
Gene expression
Pro inflam molecule secretion
Free radical production
