Obesity and insulin resistance

Question 1

What does insulin resistance mean?

Answer 1

A reduced sensitivity to insulin

Question 2

What are the causes of insulin resistance?

Answer 2

• Physiological: pregnancy and stress (cortisol and adrenaline contribute to IR) (and progesterone through growth hormone in entire bitches)
• Pathological: obesity, hereditary predisposition, endocrinopathies e.g. acromegaly and hyperadrencorticism

Question 3

Describe compensated insulin resistance

Answer 3

Obesity associated- normal concentrations of insulin are unable to remove glucose from the blood stream, pancreas secretes more insulin leading to hyperinsulinaemia (blood insulin/ glucose)

i.e. glucose is still controlled as they produce more insulin

Question 4

Describe uncompensated insulin resistance

Answer 4

Obesity associated- beta cell exhaustion (glucose toxicity)-can no longer maintain the insulin levels required.
When it gets too high it exceeds renal threshold and causes glucosuria..

Question 5

Describe the impact of type 2 diabetes mellitus on insulin resistance

Answer 5

Can follow uncompensated insulin resistance when pancreatic failure and hyperglycaemia lead to glucosuria and PUPD

Question 6

What are the molecular causes of insulin resistance?

Answer 6

• Inadequate number of insulin receptors
• Defective insulin receptor structure (have less affinity for insulin)
• Defective cell signalling pathway
• Defective with translocation of GLUT 4 transport proteins
• Problems with translocation of GLUT 4 to the membrane
• Interference with the function of GLUT 4

Question 7

How can you assess the amount of body fat?

Answer 7

• BCS
• Ultrasound to measure subcut fat (on the rump)
• Bioelectrical impedance
• Dual energy x-ray absorptiometry (DEXA): shows up body fat content

Question 8

Explain the difference between hypertrophy and hyperplasia of adipocytes

Answer 8

Hypertrophy: expansion of adipocytes
Hyperplasia: increased number of adipocytes

Question 9

Where are the common sites of accumulation for body fat?

Answer 9

• Subcut adipose tissue
• Visceral/ abdominal adipose
• Neck (horses)

Question 10

What is lipotoxicity theory?

Answer 10

Once the adipose tissue storage capacity has been reached, blood free fatty acid levels increase, they travel to other tissues e.g. liver/ skeletal muscle where they cause lipotoxicity. This is caused by the excessive levels of lipids in the cytoplasm disrupting normal cell function as signal pathways are interrupted. Insulin resistance worsens the problem as it encourages lipolysis thus increasing the movement of FFAs into circulation.

Question 11

What is proinflammatory theory?

Answer 11

Stressed adipocytes release adipokines (a cytokine)- this induces a proinflammatory state which alters intracellular signalling and leads to insulin resistance.

Question 12

What is the adipokine theory?

Answer 12

Obesity alters the balance of adipokines produced by adipocytes. Adiponectins normal role is to promote insulin activity, hence decreased adiponectin (in obese animals) normally leads to insulin resistance

Question 13

Describe how obesity is an inbalance

Answer 13

• Anabolic/ catabolic imbalance
• Faster input into storage pool: more fatty acids from diet, fat from carbohydrates
• Slower output from storage pool: lower demand (overfed and under exercised) and differences in metabolic efficiency

Question 14

What are the consequences of insulin resistance regarding glucose?

Answer 14

• Glucose: less glucose being moved into tissues because less GLUT 4 so tendency for hyperglycaemia. Gluconeogenesis is enhanced- because there isn’t enough insulin to supress gluconeogenesis in the liver.

Question 15

What are the consequences of insulin resistance regarding lipids?

Answer 15

-Lipid: increased lipolysis (adipose tissue)- insulin normally dampens the activity of HSL. Under insulin resistance HSL activity is’t supressed so fat doesn’t stay in the adipose tissue. Lipolysis is triggered by cortisol and glucagon (hence problem with cushings), higher blood free fatty acid levels

Question 16

What are the consequences of IR regarding protein?

Answer 16

Protein: amino acids used for gluconeogenesis - insulin normally enhances uptake of Aa by tissues, IR inhibits this process and Aa used to produce new glucose.

Question 17

What is the glucose tolerance test?

Answer 17

A dynamic test- it sees how much insulin is being produced and how effective that insulin is at bringing the glucose back under control.
Techincally put: it tests the ability to bring blood glucose level back to baseline (glucose tolerance) and determines how much insulin must be secreted to accomplish this

Question 18

What is seen in horses with ?

Answer 18

High levels of insulin and glucose. Primary disorder is insulin resistance. The most common clinical sign= laminitis.

Question 19

What are the 2 endocrinopathies that can cause IR?

Answer 19

• Hyperadrenocorticism

- Acromegaly (GH excess)