Systems biology course 2018 Uri Alon - Lecture 8 C - Dynamic Compensation

Summary

The script delves into the dynamics of glucose and insulin in the body, explaining how insulin resistance can lead to an increase in glucose levels. It discusses the concept of dynamic compensation, where the body adjusts to maintain a steady state despite changes in parameters like insulin sensitivity. The talk also touches on the phenomenon of glucose toxicity and its role in diabetes, highlighting the balance between robust control systems and the risk of mutant cell takeover. The speaker explores the evolutionary purpose of glucose toxicity as a defense against rogue cells and the implications for understanding diabetes and aging.

Takeaways

• 📈 Glucose levels increase immediately due to insulin, leading to cell proliferation until a steady state at 5 millimolar is reached.
• 🔄 Insulin resistance, common in obesity, results in higher glucose and insulin levels, altering the body's compensatory mechanisms.
• 🔄 Dynamic compensation allows the body to maintain normal glucose dynamics despite changes in insulin sensitivity.
• 🔍 The concept of 'steady state' is crucial, where the number of cells dividing and dying is balanced to maintain glucose levels.
• 🧬 The body's feedback loops, like the one involving insulin and glucose, are essential for maintaining homeostasis and can be modeled mathematically.
• 📉 In the presence of insulin resistance, the body compensates by increasing insulin production to maintain glucose tolerance, despite the need for higher insulin levels.
• 🚫 Glucose toxicity occurs when glucose levels are too high, leading to cell death and a vicious cycle that can result in type-2 diabetes.
• ⏳ Aging affects cell proliferation rates, which in turn influences the position of stable and unstable fixed points in glucose dynamics, increasing the risk of diabetes.
• 🧬 Glucose toxicity serves an evolutionary purpose by acting as a selective pressure against cells with mutations that misread glucose levels, thus protecting against uncontrolled cell proliferation.
• 🔄 The body's systems are designed to balance the risk of mutant cell takeover and the onset of diseases like diabetes, influenced by genetic background and lifestyle.

Q & A

What happens to glucose levels in the body when insulin resistance occurs?

When insulin resistance occurs, glucose levels initially increase because the body's cells do not respond effectively to insulin. This leads to a higher glucose concentration in the blood.

How does the body compensate for insulin resistance?

The body compensates for insulin resistance by increasing the number of beta cells, which produce more insulin to try to bring glucose levels back to normal.

What is the role of the 5 millimolar glucose level in cell division?

The 5 millimolar glucose level is a critical threshold for beta cells to stop dividing. When glucose levels reach this point, cell proliferation halts.

What is dynamic compensation in the context of the body's response to insulin resistance?

Dynamic compensation refers to the body's ability to maintain the same physiological response to meals despite changes in parameters like insulin sensitivity, through adjustments in the number of beta cells and insulin production.

How does the body's response to glucose change after insulin resistance has developed?

After insulin resistance has developed, the body initially shows an abnormal glucose tolerance test due to the beta cells not having expanded enough to compensate. However, once a new steady state is reached, the glucose tolerance test becomes indistinguishable from before, but with higher insulin levels.

What is the significance of the hyperbolic relationship between insulin and glucose levels?

The hyperbolic relationship signifies that for every unit increase in insulin, there is a corresponding increase in glucose uptake and utilization, which helps maintain glucose homeostasis.

What is glucose toxicity and how does it relate to diabetes?

Glucose toxicity refers to the phenomenon where high glucose levels lead to the death of beta cells. This can result in a vicious cycle where less insulin is produced, leading to even higher glucose levels, which is characteristic of type-2 diabetes.

How does aging affect the body's ability to handle glucose?

Aging typically reduces cell proliferation rates, which can cause the fixed points in glucose regulation to shift, making it easier for glucose levels to cross the threshold into glucose toxicity.

What is the evolutionary purpose of glucose toxicity?

Glucose toxicity serves as a mechanism to eliminate cells that have mutations causing them to misread glucose levels, which could otherwise proliferate uncontrollably and disrupt glucose homeostasis.

How does the body balance the risk of mutant cell takeover and diabetes?

The body balances the risk of mutant cell takeover and diabetes by optimizing the levels of glucose toxicity and the rate of cell proliferation, which can be influenced by genetic factors and lifestyle choices.