Endocrine control of metabolism Flashcards

1
Q

Give an overview of energy metabolism

A

On image

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2
Q

What nutrients are circulated and what nutrients are stored?

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

Stored:
Glycogen
Triglycerides (TG, TAG)
Body proteins

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3
Q

What is the normal blood glucose concentration?

A

Around 5 mmol L-1

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4
Q

Define hyperglycemia and hypoglycemia?

A

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

Hypoglycemia: ultimately coma and death
< ~2.5 mmol L-1 is critical

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5
Q

How much glucose do the brain and skeletal muscle use?

A

Brain = 30mmol hr -1

Skeletal muscle = 300mmol hr-1

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6
Q

Where do we get glucose from?

A

Diet

Organs that can export glucose into the circulation

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7
Q

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

A

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

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8
Q

What happens to nutrients in the fasting and absorptive phases?

What does insulin promote?

What hormones promote nutrient release?

How does insulin stimulate nutrient storage?

A
  1. Storage of nutrients in the absorptive phase (fed state)
    Release of nutrients in the fasting phase (between meals)
  2. Insulin: promotes storage, decreases plasma glucose
  3. Glucagon
    Adrenaline (epinephrine)
    Cortisol, growth hormone (somatotrophin)

Uptake of glucose by skeletal muscle, adipose and other tissues

Glycogen synthesis in liver, skeletal muscle,

Uptake of FA and amino acids

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9
Q

How does insulin inhibit nutrient release?

A

Inhibits nutrient release

Inhibits release of glucose from liver (hepatic glucose production)

Inhibits fat and protein breakdown (lipolysis and proteolysis)

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10
Q

Where is glucagon produced and what does it stimulate?

Where is adrenaline produced and what does it stimulate?

What does cortisol stimulate?

I.e Glucagon, Adrenaline and Cortisol

A

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: release of FA from adipose tissue stores

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

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11
Q

What metabolic pathways serve as energy storage?

A

Glycogenesis
Synthesis of glycogen from glucose

Lipogenesis
Synthesis of FA from acetyl CoA

Triglyceride synthesis
Esterification of FA for storage as TG

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12
Q

What metabolic pathways serve as energy release?

Define: 
Glycogenolysis
Gluconeogenesis  
Lipolysis 
Beta-oxidation
Ketogenesis
A

Glycogenolysis
Release of glucose from glycogen stores

Gluconeogenesis
De novo synthesis of glucose from non-carbohydrate substrates

Lipolysis
Release of FA from TG breakdown

Beta-oxidation
FA to Acetyl Co A

Ketogenesis
Production of ketone bodies from Acetyl CoA

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13
Q

Describe the metabolic response to hypoglycemia

A

On image

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14
Q

What are the short, medium and long term defences against hypoglycaemia?

A

In the short-term:
Glucagon
Epinephrine
Sympathetic NS

In the medium-term:
Ketogenesis: fat reserves can provides 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

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15
Q

What are the defences against hyperglycemia?

What is type 1 DM?

What is type 2 DM?

A

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

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16
Q

Describe the metabolic pathway involving glucose and the effects of stimulating insulin

A

On image

17
Q

What are the major metabolic pathways in adipose tissue?

A

On image

18
Q

What is gluconeogenesis stimulated by?

What does gluconeogenesis form?

A

Stimulated by glucagon and inhibited by insulin

Amino acids are converted to ACETYL COA, pyruvate or enter the TCA cycle. It is then converted to oxaloacetate then to phosphoenol pyruvate then to glucose 6 phosphate

19
Q

Describe the process of fatty acid metabolism in the liver

A

On image

20
Q

Describe the process of fat metabolism and ketogenesis

What can fatty acids be used/ turned into when entering the liver?

What does beta-oxidation of fatty acid produce?

What happens to the product of beta-oxidation?

What 2 ketones are formed during ketogenesis?

How can ketones be used to produce energy?

A

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 Co A
Acetyl Co A may enter TCA cycle, or enter ketogenesis, depending on nutritional / hormonal status
Ketogenesis: synthesis of acetoacetate and hydroxybutyrate (ketone bodies) from Acetyl Co A
Ketone bodies are freely transported in blood stream, reconverted back to acetyl CoA, in brain and other tissues, and metabolised in TCA cycle for energy

21
Q

Describe the process of ketogenesis

What happens when Acetyl CoA combines with oxaloacetate (OAA)?

What can this enter and then do?

What is OAA also a substrate for?

What happens in the absence of OAA?

What can lots of ketone bodies cause? RESP

A

In the liver, oxidation of fatty acids and gluconeogenesis can compete for substrates

  • Beta-oxidation of FA produces acetyl Co A, 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 Co A builds up and is funnelled into ketogenesis

Ketone bodies are acids: excess in circulation overwhelm buffering capacity of blood, leading to metabolic acidosis

22
Q

What occurs in diabetic ketoacidosis?

A

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

On slides