Lecture 7 - Insulin

Question 1

Human Brain size

Answer 1

• Larger than any other mammal (body size to brain size)
  
  • Known as Encephalization Quotient
• Additional evidence: we have smaller muscles to body size and organs
  
  • Suggests a fitness trade-off between energy to make brain and other organs/functions

Question 2

Energy Consumption of Brain from birth to adult

Answer 2

• In newborns, 87% of energy is spent on brain development
• Resting Metabolic Rate (RMR) is high even at rest in general
• Metabolism % lowers over time but still takes up at least 1/4 of total energy
  
  • Brain only 1/20th of weight, takes 25% energy

Question 3

What kind of energy does the brain use?

Answer 3

• Glucose from carbs = preferred
  
  • Protein converts it when available
    
    • Protein was not readily accessible in ancestral past
  • During starvation, ketones (converted from fat) used
    
    • Brain gets priority in energy during starvation. Other organs have some protien stores it can use but will reduce in size (get sacrificed)

Question 4

Insulin

Answer 4

• Ancient, over 2 billion years old
• Promotes growth in animals
• Regulates uptake/consumption of glucose
• Insulin influences how bacteria grows in the body
  
  • Some bacteria grow faster, some slower
• Pancrease produces insulin
  
  • In reponse to glucose in bloodstream
  • Signal tells tissue to take up glucose from the blood
• Insulin can be stored as glycogen, convert to pyruvates and fatty acids
• Increases consumption of activated macrophages\

Question 5

Insulin Resistance

(how is it achieved)

Answer 5

• Resistance happens everywhere but the brain
• Brain is preserved during starvation because it’s resistant to insulin
  
  • Resistant tissues must burn fat to satisfy metabolism
  • Resistance to selected tissues evolved to help us allocate energy for different situations
    
    • Because brain is priority for most situations, insulin resistance exists in other tissues
• 1 receptor for insulin (InsR)
  
  • Cells sensitive to insulin bind to receptor and triggers glucose transport
  • Resistance caused by decreased receptor expression
    
    • Therefore, not as much glucose uptake
      *

Question 6

Systemic IR vs. Local IR

Answer 6

• Systemic IR: insulin resistance throughout body but not brain
• Local IR: Insulin resistance locally for specific tissues

Question 7

Macrophages

(T/B-Cells)

Answer 7

• Macrophages consume insulin and increase phagocytic properties
• Macrophages engulf bacteria through pagocytosis (engulf/inject/emulsify)
  
  • Very expensive to activate
  • Activated macrophages consume same amount of energy as maximally functioning heart tissue
  • Rely on glycolysis and therefore need energy at a faster rate
• T/B cells cause increased expression of INsR
  
  • Increased expression of InsR from T/B cells require more energy to respond to infection
  • Insulin promotes the groth of virally activated T-cells
• Insulin is causing the growth of T-cells, and antibodies supress growth (additional evidence)

Question 8

3 types of macrophages

Answer 8

1. RES: Resident macrophages: no immune activation
2. TG: cause macrophage migration to peritoneal immune activation
3. BCG: infectious agent used to elicit full immune response
   
   1. Uses the most InsR

Question 9

Innate vs. Adaptive Immune System

Answer 9

• Adaptive: AG contacts macrophage, activates macrophage in response to infection, produces antibodies, t-cells active causing more insulin production

Question 10

During Infection

Answer 10

• Cytokines trigger IR in organs bu tnot brain
  
  • Insulin sensitivity is increased in immune tissue
• Energy allocated to where it is most needed
• In starvation, immune tissue becomes resistant

Question 11

Why is it not good for glucose to circulate in excess?

(Type 1/2 Diabetes)

Answer 11

• Glucose can stick to your red blood cells
  
  • Occurs from an increased modified carb diet
• Insulin sends extra glucose to the liver where fat builds up
  
  • Cause of type 2 diabetes
• Type 1: Pancreatic islet cells hit by infection and can no longer produce insulin
• “Thrifty genes hypothesis

Question 12

3 situations for insulin responses

Answer 12

• During energetic stress, body makes (tissue-specific) tradeoffs to how energy is located
• During infection, immune tissues have increased insulin, but other organs have IR
• During starvation, immune is also sacrificed but not he brain