Endocrine Control & Metabolism

Question 1

What is the significance of keeping plasma glucose at 5mmol/l?

Answer 1

Brain depends on glucose metabolism

Question 2

What is the source of our body glucose?

Answer 2

• diet
• organs that can export glucose into the circulation

Question 3

What prevents plasma glucose surging after a meal and plummeting between meals?

Answer 3

Hormones regulate the integration of carbohydrate, fat and protein metabolism

Question 4

What are the two phases of metabolism?

Answer 4

• storage of nutrients in the absorptive stage (fed state)
• release of nutrients in the fasting phase (between meals)

Question 5

List some counter-regulatory hormones (those that promote nutrient release, raise plasma glucose).

Answer 5

• glucagon
• adrenaline
• cortisol, growth hormone

Question 6

What are some major effects of insulin on stimulating nutrient release?

Answer 6

• Uptake of glucose by skeletal muscle, adipose and other tissues
• Glycogenesis in the liver and skeletal muscle
• Uptake of fatty acids and amino acids

Question 7

What are some major effects of insulin on inhibiting nutrient release?

Answer 7

• Inhibits hepatic glucose production
• Inhibits lipolysis and proteolysis

Question 8

What are some effects of the counter-regulatory hormones? PART 1

Answer 8

Stimulate pathways leading to energy release.

GLUCAGON: has principal effects in the liver
- stimulates hepatic glucose production

Question 9

What are some effects of the counter-regulatory hormones? PART 2

Answer 9

ADRENALINE (and sympathetic NS)
stimulates hepatic glucose production
stimulates lipolysis (release of fatty acids from adipose tissue stores)

CORTISOL:
- same as adrenaline but stimulates proteolysis (NOT LIPOLYSIS)

Question 10

What are some metabolic pathways serving as energy storage?

Answer 10

GLYCOGENESIS
LIPOGENESIS: the synthesis of fatty acids from Acetyl CoA
TRIGLYCERIDE SYNTHESIS: the esterification of fatty acids for storage as triglycerides

Question 11

What are some metabolic pathways serving as energy release? PART 1

Answer 11

GLYCOGENOLYSIS
GLUCONEOGENESIS: de novo synthesis of glucose from non-carbohydrate substrates
LIPOLYSIS: release of fatty acids from triglyceride breakdown

Question 12

What are some metabolic pathways serving as energy release? PART 2

Answer 12

β-OXIDATION: the conversion of fatty acids from Acetyl CoA
KETOGENESIS: the production of ketone bodies from Acetyl CoA

Question 13

What is the metabolic response to hypoglyceamia?

Answer 13

• Plasma glucose is detected in the pancreas
• Increase in glucagon secretion from alpha cells.

Question 14

What are the body’s defences against hypoglycemia in the short term?

Answer 14

• glucagon
• adrenaline
• sympathetic NS

Question 15

What are the body’s defences against hypoglycemia in the medium term?

Answer 15

• Ketogenesis: the fat reserves provide a partial substitute for glucose

Question 16

Why is ketogenesis useful?

HINT - Think about what ketogenesis produces and what would happen if ketogenesis were to fail

Answer 16

• Produces fatty acids
• If ketogenesis didn’t happen, skeletal muscle would be broken down to form amino acid substrates for gluconeogenesis

Question 17

What are the body’s defences against hypoglycemia in the long term?

Answer 17

• Cortisol stimulates proteolysis to supply amino acid substrates for gluconeogenesis.

Question 18

What are the body’s defences against hyperglyceamia?

Answer 18

INSULIN
- Stimulates glucose uptake by tissues
- Inhibits hepatic glucose production

Question 19

What are the two types of hyperglycaemia?

Answer 19

TYPE I Diabetes: insulin deficiency
TYPE II Diabetes: insulin insufficiency combined with insulin resistance

Question 20

What are some major insulin-sensitive tissues, and what processes are affected by insulin? PART 1

Answer 20

INSULIN STIMULATES:
- LIVER: glycogenesis, glycolysis, lipogenesis
- ADIPOSE TISSUE: glucose uptake, free fatty acid uptake, lipogenesis
- MUSCLE: glucose uptake, amino acid uptake, glycogenesis

Question 21

What are some major insulin-sensitive tissues, and what processes are affected by insulin? PART 2

Answer 21

INSULIN INHIBITS:
- LIVER: glycogenolysis, gluconeogenesis
- ADIPOSE TISSUE: lipolysis

Question 22

Describe major metabolic pathways in adipose tissue during positive energy balance.

Answer 22

Insulin stimulates uptake

Question 23

Describe major metabolic pathways in adipose tissue during negative energy balance.

Answer 23

• Counter-regulatory hormones stimulate lipolysis and the release of FFA to circulation.
• Distributed to tissues for uptake and energy metabolism.

Question 24

Describe glucose and amino acid metabolism in the liver. PART 1

Answer 24

Ketogenic amino acids (converted into Acyl CoA or Aceto-Acyl CoA) can give rise to ketone bodies or fatty acids (KETOGENESIS).

Question 25

Describe glucose and amino acid metabolism in the liver. PART 2

Answer 25

- Glucogenic amino acids are converted into pyruvate or citric acid cycle intermediates. - Synthesis of glucose is possible via phosphoenol pyruvate (PEP). - Oxaloacetate is converted to PEP by PEP carboxykinase (PEPCK).

Question 26

Describe fatty metabolism in the liver (how insulin inherently inhibits β-oxidation). PART 1

Answer 26

In β-oxidation, fatty acids are converted to Acyl-CoA, then to Acetyl-CoA (in the mitochondria). - Acetyl CoA can be used to generate ATP via the TCA. - If in excess, Acetyl-CoA goes instead into ketogenesis.

Question 27

Describe fatty metabolism in the liver (how insulin inherently inhibits β-oxidation). PART 2

Answer 27

- Glucose is converted to Acetyl CoA. - If in excess and in the presence of insulin, Acetyl CoA goes instead into lipogenesis, back to fatty acids (which will then be esterified to form triglycerides).

Question 28

Describe fatty metabolism in the liver (how insulin inherently inhibits β-oxidation). PART 3

Answer 28

- First intermediate in lipogenesis is Malonyl-CoA - Malonyl-CoA inhibits CPT (carnitine-palmitoyl transferase), which is required to get fatty Acyl-CoA into mitochondria for oxidation (or ketogenesis).

Question 29

Describe how fat metabolism and ketogenesis relate. PART 1

Answer 29

- Fatty acids entering the liver are esterified for transport and storage as triglycerides, or enter the mitochondria for β-oxidation.

Question 30

Describe how fat metabolism and ketogenesis relate. PART 2

Answer 30

- β-oxidation of fatty acids produces Acetyl-CoA. - Acetyl-CoA may enter the TCA cycle, or enter ketogenesis, depending on the body’s nutritional/ hormonal status.

Question 31

Describe how fat metabolism and ketogenesis relate. PART 3

Answer 31

- Ketogenesis is the synthesis of ketone bodies from AcetylCoA. - Ketone bodies are freely transported in the blood stream, reconverted back to Acetyl-CoA, in the brain and other tissues, and metabolised in the TCA cycle for energy.

Question 32

Describe diabetic ketoacidosis.

Answer 32

- In insulin deficiencies (ie. type I diabetes mellitus), buffering capacity is overwhelmed. - Decreased serum bicarbonate, which leads to diabetic ketoacidosis (normally, ketones, which are acids, are buffered by the blood).