Endocrine control of metabolism

Question 1

What are the circulating nutrients?

Answer 1

Glucose
Fatty acids (FFA, NEFA)
Amino acids
Ketone bodies
Lactate

Question 2

What are the stored nutrients?

Answer 2

Glycogen
Triglycerides (TG, TAG)
Body proteins

Question 3

What is the normal level of plasma glucose?

Answer 3

5 mmol L-1

Question 4

What is too low glucose levels called?

Answer 4

Hypoglycemia: ultimately coma and death

< ~2.5 mmol L-1 is critical

Question 5

What is too high glucose levels called?

Answer 5

Hyperglycemia: chronic exposure to raised glucose concentrations leads to protein damage via non-enzymatic glycation

Question 6

What is the 60/40/20 rule?

Answer 6

60% of body weight is water
40% of body weight is intracellular water
20% of body weight is extracellular water

Question 7

What are the sources of plasma glucose?

Answer 7

• Diet
• Organs that can export glucose into the circulation

Diet: up to 3000 mmol day-1

Question 8

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

Answer 8

Hormones regulate the integration of carbohydrate, fat and protein metabolism to maintain constant plasma glucose levels.

Question 9

What are the two phases of metabolism?

Answer 9

Absorptive phase (fed state) - storage of nutrients
Fasting phase (between meals) - release of nutrients

Question 10

What hormones regulate metabolic pathways promoting energy storage or release?

Answer 10

Insulin: promotes storage, decrease in plasma glucose levels

Counter-regulatory hormones: promote nutrient release, raise plasma glucose.

• Glucagon
• Adrenaline
• Cortisol, growth hormone (somatropin)

Question 11

What are the major effects of insulin?

Answer 11

Stimulates nutrient storage:

• Uptake of glucose by skeletal muscle, adipose and other tissues
• Glycogen synthesis in liver and skeletal muscle
• Uptake of FA and amino acids

Inhibits nutrient release:

• Inhibits release of glucose from liver (hepatic glucose production)
• Inhibits fat and protein breakdown (lipolysis and proteolysis)

Question 12

What are the major effects of counter-regulatory hormones?

Answer 12

Stimulate pathways leading to energy release

Glucagon: principal effects in liver
-Stimulates hepatic glucose production

Adrenaline (and sympathetic NS)

• Stimulates hepatic glucose production
• Stimulates lipolysis: a release of FA from adipose tissue stores

Cortisol

• Stimulates hepatic glucose production
• Stimulates proteolysis: a release of amino acids from body proteins (skeletal muscle)

Question 13

What are the metabolic pathways for energy storage?

Answer 13

Glycogenesis
-Synthesis of glycogen from glucose
Lipogenesis
-Synthesis of FA from acetyl CoA
Triglyceride  synthesis
-Esterification of FA for storage as TG

Question 14

What the are metabolic pathways for energy release?

Answer 14

Glycogenolysis
-Release of glucose from glycogen stores
-De novo synthesis of glucose from non-carbohydrate substrates
Lipolysis
-Release of FA from TG breakdown
Beta-oxidation
-FA to Acetyl CoA
Ketogenesis
-Production of ketone bodies from Acetyl CoA

Question 15

What senses changes in blood glucose levels?

Answer 15

Endocrine cells in the pancreas, cells in the brain

Question 16

What are the metabolic responses to hypoglycemia?

Answer 16

Low glucose detected by the endocrine cells in the pancreas and it releases glucagon and inhibits insulin secretion. glucagon stimulates the liver to increase hepatic glucose output, both glycogenolysis and gluconeogenesis.
Brian cells will also detect and activate the sympathetic pathway and activate adrenal medulla which will also increase circulating epinephrine.

Question 17

What are the defences against hypoglycemia?

Answer 17

In the short-term

• Glucagon
• Epinephrine
• Sympathetic NS

In the medium-term
-Ketogenesis: fat reserves can provide a partial substitute for glucose, sparing muscle tissue from the destruction that would otherwise be needed to provide amino acid substrates for gluconeogenesis

In the long-term
-Cortisol stimulates proteolysis to supply amino acid substrates for gluconeogenesis

Question 18

What are the defences against hyperglycemia?

Answer 18

Insulin
-Stimulates glucose uptake by tissues
-Inhibits hepatic glucose production
Lack of insulin action leads to hyperglycaemia, diabetes mellitus
-Type 1 DM: insulin deficiency
-Type 2 DM: insulin insufficiency combined with insulin resistance

Question 19

What does insulin stimulate?

Answer 19

Liver

• glycogenesis
• glycolysis
• lipogenesis

Adipose tissue

• glucose uptake
• free fatty acid uptake
• lipogenesis

Muscle

• glucose uptake
• amino acid uptake
• glycogenesis

Question 20

What does insulin inhibit?

Answer 20

Liver

• glycogenolysis
• gluconeogenesis

Adipose tissue
-Lipolysis

Question 21

Explain fat metabolism and ketogenesis

Answer 21

Fatty acids entering the liver may be esterified for transport and storage as TG, or enter mitochondria for beta-oxidation

Beta-oxidation of FA produces acetyl CoA

Acetyl CoA may enter TCA cycle, or enter ketogenesis, depending on the nutritional/hormonal status

Ketogenesis: synthesis of acetoacetate and hydroxybutyrate (ketone bodies) from Acetyl Co A

Ketone bodies are freely transported in the bloodstream, reconverted back to acetyl CoA, in the brain and other tissues, and metabolised in TCA cycle for energy

Question 22

What is ketogenesis?

Answer 22

In the liver, oxidation of fatty acids and gluconeogenesis can compete for substrates
Beta-oxidation of FA produces acetyl CoA, which combines with oxaloacetate (OAA) to form citrate, entering the TCA cycle for complete oxidative phosphorylation
However, OAA is also used as a substrate in gluconeogenesis
In absence of sufficient OAA, acetyl CoA builds up and is funnelled into ketogenesis
Ketone bodies are acids: excess in circulation overwhelm buffering capacity of blood, leading to metabolic acidosis

Question 23

What is diabetic ketoacidosis?

Answer 23

Express production fo ketone bodies which are mildly acidic
In insulin deficiency (i.e. type 1 diabetes mellitus) the buffering capacity is overwhelmed
Decreased serum bicarbonate
Diabetic ketoacidosis
Normally ketones (acids) are buffered by the blood
deep sighing (Kussmaul) respiration
in the absence of insulin, Acetyl CoA turns into ketone bodies instead of making citrate with oxaloacetate.