Human metabolism lecture 2

Question 1

Diabetes

Answer 1

• Fasting hyperglycaemia + postprandial hyperglycaemia
• T1D = defect in B cells of pancreas
• T2D = insulin resistance, B cell secrete ↑

Question 2

Changes to carbohydrate metabolism

Answer 2

• Liver overproduces glucose from gluconeogenesis

- Muscle underutilises

Question 3

Change to fat metabolism

Answer 3

• Adipose overproduces FA as lipolysis x inhibited
• ↑ FA stimulates oxidation in muscle, inhibits glucose ox through glucose-FA cycle
• ↑ FA also stimulates ketone production
• ↑ TAG, ↓ HDL

Question 4

Insulin resistance

Answer 4

• E intake > expenditure = surplus E stored as TAG in adipose
• If x store more, TAG accumulate in muscle
• PKCe sensitive to stimulation by DAG, recruited to membrane + phosph IR (imparts P13K/PKB)
• But TAG accumulate not DAG

Question 5

Paradox in liver metabolism

Answer 5

• In diabetes, liver overproduces glucose
• Explained by IR in gluconeogenesis
• BUT glycogen breakdown x contribute
• BUT liver produces VLDL TAG

Question 6

Hypothesis : liver metabolism controlled by precursor supply

Answer 6

• Gluconeogenesis = controlled by glycerol from adipose + aa from muscle
• IR adipose overproduce glycerol + muscle aa
• So can be explained (x involve liver IR)
• TAG production = controlled by FA from adipose + esterification by glycerol-3-P made by IR adipose

Question 7

Hypothesis: liver insulin resistance is selective x global

Answer 7

• Insulin inhibits transcription of gluconeogenic E
• In diabetes this = IR so transcription of key E x inhibited + glucose overproduced
• Transcription of key E of FA + esterification stimulated by insulin which is overactive in IR
• But x gives inside

Question 8

Potential mechanism for IR

Answer 8

• E intake > expenditure, E stored as TAG in adipose
• When exceeded, ectopic fat causes IR
• When B cells fail to compensate, abnormal carb metabolism results
• In muscle = defective glucose uptake
• In liver = glucose overproduced + TAGs by adipose