Absorptive State

Question 1

What is the absorptive state?

Answer 1

• Food in GIT
• Nutrients being absorbed into blood + lymph

Question 2

What is the post-absorptive state?

Answer 2

• Fasting state
• Nutrients not being absorbed

Question 3

What blood system to absorbed nutrients enter and where is the first organ they visit?

Answer 3

• Portal blood
• Liver

Question 4

Hormone-sensitive tissues of energy metabolism

Answer 4

• Liver
• Muscle
• Adipose tissue

Question 5

What causes the switch from the post-absorptive to absorptive state?

Answer 5

Increased glucose + insulin in blood

Question 6

What is the transporter responsible for beta cell glucose uptake?

Answer 6

GLUT-2

Question 7

Is GLUT-2 insulin sensitive or non-insulin sensitive?

Answer 7

Non-insulin sensitive

Question 8

What does glucose entry through GLUT-2 trigger?

Answer 8

• Generation of ATP from glucose metabolism
• Ca2+ influx

Question 9

What does the Ca2+ influx from GLUT-2 glucose transport cause?

Answer 9

Insulin exocytosis

Question 10

What transporter moves glucose into tissues of the body requiring glucose?

Answer 10

GLUT-4

Question 11

Is GLUT-4 insulin sensitive or non-insulin sensitive?

Answer 11

Insulin sensitive

Question 12

Feedback control of insulin after a meal

Answer 12

• Blood glucose concentration increases
• Insulin secretion stimulated
• Glucose uptake into cells (GLUT-4)
• Blood glucose concentration falls
• Stimulus for insulin secretion removed
• Blood insulin concentration falls

Question 13

How does insulin regulate access of glucose into muscle and fat?

Answer 13

• GLUT-4 stored within the cell
• Insulin stimulates translocation to plasma membrane

Question 14

General action of insulin in the liver

Answer 14

• Glycogen synthesis
• Glycolysis

Question 15

General action of insulin in muscle

Answer 15

• Glucose uptake
• Glycogen synthesis
• Glycolysis

Question 16

General action of insulin in adipose tissue

Answer 16

• Glucose uptake
• Glycolysis
• Triglyceride synthesis

Question 17

Types of reactions in the post-absorptive state

Answer 17

• Glucose-supplying reactions (make glucose)
• Glucose-sparing reactions (make FA’s + ketone bodies instead)

Question 18

Glucose-supplying reactions producing glucose in the liver

Answer 18

• Glycogenolysis
• Gluconeogenesis

Question 19

Control of glucose-supplying reactions

Answer 19

• Fall in insulin levels
• Increase in other hormones:
  > Epinephrine (increase glycogen breakdown in muscle, adipocytes + liver)
  > Glucagon (increase glycogen breakdown + gluconeogenesis in liver)
  > Cortisol (increase gluconeogenesis in liver + decrease glucose uptake)
  > Growth hormone (decrease glucose uptake)

Question 20

What is beta oxidation?

Answer 20

Process by which fats are used to liberate energy

Question 21

How does beta oxidation liberate energy?

Answer 21

• After cycle fatty acid is 2 carbons shorter –> acetyl CoA used in Krebs for energy
• Energy released via FADH2 + NADH at some steps

Question 22

Classification of type 1 diabetes

Answer 22

• Young onset
• Destruction of beta cells –> loss of insulin
• Severe metabolic derangement due to inability to utilise glucose
• Switch to other fuels (AAs, lipids) leads to marked weight loss + metabolic disturbances (hyperlipidaemia, ketoacidosis)

Question 23

Classification of type 2 diabetes

Answer 23

• Prevalence increases with age
• Insulin levels normal/high but reduced action (ie. resistance)
• Treated with lifestyle, tablets or insulin
• Less severe metabolic derangements
• Long-term damage due to high glucose levels + lipid abnormalities

Question 24

Effect diabetes has on processes in the liver

Answer 24

• Decreased glycogen synthesis
• Increased glycogenolysis

Question 25

Effect diabetes has on processes in adipose tissue

Answer 25

- Decreased glucose uptake - Increased lipolysis

Question 26

Effect diabetes has on processes in muscle

Answer 26

- Increased extracellular glucose - Breakdown of protein to AAs for gluconeogenesis (muscle wasting)

Question 27

How does diabetes cause ketoacidosis?

Answer 27

- Increased lipolysis leads to increased circulating FAs - These are directed to the liver to be used in beta-oxidation, liberating energy + acetyl CoA - High acetyl CoA levels inhibit Krebs cycle and acetyl CoA is pushed towards ketogenesis - Ketones are then used as energy source in extra-hepatic tissues - Transported via blood, and acidic nature of ketones leads to acidosis

Question 28

Clinical features of uncontrolled diabetes

Answer 28

- Polyuria/polydipsia - Dehydration - Blurred vision - Infections - Weight loss (muscle + fat wasting) - Ketosis - Confusion - Coma

Question 29

Treatment of uncontrolled diabetes

Answer 29

- Rehydration with intravenous saline - Insulin (infusion or s/c / i/m injections) - Monitor +/- correct serum electrolytes (potassium disturbance common) - Treat underlying cause (eg. infection)

Question 30

Why is potassium disturbance common in uncontrolled diabetes?

Answer 30

Insulin normally activates Na+/K+ ATPases causing flux of potassium into cells

Question 31

Microvascular complications of diabetes

Answer 31

- Retinopathy - Nephropathy - Neuropathy

Question 32

Macrovascular complications of diabetes

Answer 32

- Atherosclerosis - Strokes - Heart attacks - Peripheral vascular disease - Hyperlipidaemia - Hepatic steatosis

Question 33

Long-term treatment of diabetes

Answer 33

- Reduction in vascular risk: > Lipid lowering drugs > Reduced BP > Aspirin > Avoiding smoking - Tight regulation of blood glucose: > Diet > Home monitoring > Adjustment of tablets/insulin