Chapter 11 - Dynamical compensation and mutant resistance in tissues Flashcards
Name 3 challenges in tissues:
1) must contain constant size although cells divide exponentially
2) They must be able to signal other tisues with unknown parameters
3) Avoid mutant cells that can grow and overtake tissue
What function describes the overall glucose levels in te body?
G(t)
Explain the basic blood sugar/ insulin feedback system.
The system is a negative feedback system, with high blood glucose causing an increase in insulin production which then in turn reduces blood sugar levels. Can be written as:
dG/dt = m (meal) - s (insulins sensitivity) * G * I (insulin)
dI/dt = B (amount of beta cells) * q*f(G) (insulin production rate also q) - gamma (insulin degredation rate) * I
How to showthat the minimal model is not robust on the basis of s:
Take the steady state and isolate Gst using f(G) = G^2
How do we expand the simple glucose model?
By including a term that explains beta cell proliferation.
What is the basic formula for cell proliferation dynamics?
dB/dt = p(prolif)B - d(death)B
p - d can be written as mu:
dB/dt = mu*B - which is an exponential
How do we keep growth rate at 0?
Introduce new function:
mu = mu(G)
Death and growth rates of beta cells are dependent on glucose levels.
What does the BIG model stand for?
Beta-cell, insulin, glucose
What is the slow feedback loop for blood glucose?
Beta cell proliferation and death.
What is dynamical compensation?
The ability of a model to compensate for changes to a parameter.
Explain how a mutant beta cell can take over the pancreas:
If the mutant cell has a broken sensor system and thinks the glucose levels are too high, they will proliferate and secrete insulin. This will decrease blood sugar to a point where normal beta cells undergo apoptosis because the blood sugar is too low.
