Obesity and insulin resistance Flashcards
What is the progression of insulin resistance?
Insulin resistance at the start is compensated IR (the body just tells the pancreas to make more insulin) but when the pancreas cant cope with that it becomes uncompensated IR which will develop into Type 2 diabetes mellitus (NIDDM) when pancreatic failure and hyperglycaemia lead to glucosuria and PUPD.
What does compensated IR mean?
Compensated IR in horses - “normal” concentrations of insulin are unable to remove glucose from the blood stream, pancreas secretes more insulin leading to hyperinsulinaemia (i.e. compensating) but this becomes uncompensated when Beta-cell exhaustion (glucose toxicity) – can no longer maintain the insulin levels required.
What is the cause of IR at the cellular level?
Inadequate number of insulin receptors Defective insulin receptor structure Defective cell signaling pathway Defective GLUT4 transport proteins Problems with translocation of GLUT4 to the membrane Interference with the function of GLUT4
What causes an increase in body fat?
expansion of adipocytes (hypertrophy) or Increased number of adipocytes (hyperplasia)
What three theories explain why obese animals are more likely to suffer from IR?
Lipotoxicity theory
Proinflammatory theory
Adipokine theory
What is the lipotoxicity theory?
There is a limit of fat storage subcut so it is sent to the visceral tissue and when the visceral fat stores become full the fat is then sent to the liver which becomes overwhelmed and sends it into the systemic circulation and blood fatty acid levels rise and this overflows into other tissues but this will disrupt normal cell function. As lipid accumulates within myocytes, insulin signaling pathways are disrupted
Disrupted signal transduction leads to insulin resistance.
What is the proinflammatory theory?
Adipose tissues reach their capacity for fat storage
Stressed adipocytes release inflammatory cytokines (adipokines) which create a proinflammatory state
Alter intracellular signal transduction pathways leading to insulin resistance
What is the Adipokine theory?
Adipocytes produce cytokines that can be classified as hormones (adipokines)
Obesity alters the balance of adipokines produced by adipocytes
For example, adiponectin production decreases as obesity develops
Adiponectin enhances the action of insulin so lower adiponectin levels contribute to IR
What is the effect of IR on glucose?
IR causes Impaired glucose uptake into tissues but Increased glucose synthesis by the liver via gluconeogenesis
What is the effect of IR on lipid metabolism?
Increased lipolysis (adipose tissues) as insulin normally dampens down the HSL activity.
Higher blood free fatty acid levels
Lipid storage shifts toward storing in the skeletal muscle
What is the effect of IR on protein metabolism?
Insulin normally enhances uptake of amino acids by tissues (anabolic) so IR cause amino acids to be converted to glucose via gluconeogenesis
What is a glucose tolerance test?
A dynamic test used to “stress” the system to reveal inadequacies
Involves the intravenous injection of dextrose and then serial blood samples
It assesses the ability of the blood to bring glucose back to base level (should be back to normal within 2h)
What is the primary disorder in equine metabolic syndrome? What is the most common clinical sign
The primary disorder in EMS is insulin resistance
Most common clinical signs is laminitis
High levels of insulin and glucose are seen in ponies with EMS
