I've got these three, apparently independent, origins for the concept that insulin resistance is an evolutionary conserved mechanism, essential for survival but maladaptive in the modern world. What links them is the concept that an essential feature can be maladaptive. Here are the quotes:
Insulin resistance is an evolutionarily conserved physiological mechanism at the cellular level for protection against increased oxidative stress
Erol 2007
"For this reason, insulin resistance could be a physiological mechanism activated at the cellular level in response to conditions stimulating ROS production and leading to the prevention of oxidative stress, and extension of life. Concerning the whole organism, however, IR is a maladaptive process in the long term causing a diabetic state."
Insulin resistance is a cellular antioxidant defense mechanism
Erol 2007
"For this reason, insulin resistance could be a physiological mechanism activated at the cellular level in response to conditions stimulating ROS production and leading to the prevention of oxidative stress, and extension of life. Concerning the whole organism, however, IR is a maladaptive process in the long term causing a diabetic state."
Insulin resistance is a cellular antioxidant defense mechanism
Hoehn et al 2009
"For most organisms the latter [nutrient excess] is presumably quite rare or at least an intermittent phenomenon emphasizing why the current situation of constant nutrient oversupply is not easily tolerated."
"For most organisms the latter [nutrient excess] is presumably quite rare or at least an intermittent phenomenon emphasizing why the current situation of constant nutrient oversupply is not easily tolerated."
Soeters and Soeters 2012
"If we accept that insulin resistance benefits limitation of net degradation of protein in long-term starvation and stress while facilitating PPP and anaplerosis, the role of insulin resistance in overfeeding is enigmatic."
Insulin resistance is absolutely essential on a cellular basis. All insightful people agree on this.
Also, on a cellular basis, insulin *resistance* is the hallmark of cellular "fullness". It marks out a given cell as being energy replete. That's Protons.
Evolution very rarely invents anything new. If you have an organism of increasing complexity which needs to regulate its overall food intake at the macroscopic level it is not going to "invent" a food counting mechanism to decide whether a cow has eaten enough mouthfuls of grass to sustain it for the coming few hours.
No. Evolution will take a few representative cells, feed them on a representative sample of what is available, energetically, in the blood stream, and see if that energetic supply generates enough of an ROS signal to decide whether those cells have enough substrate to generate an adequate "fullness' signal. This requires an adequate level of ROS generation to resist insulin. Evolution takes the core system of ROS and converts it in to either hungry or not hungry using a set of specialised brain cells.
Insulin *resistance* (ie ROS) within the ventromedial hypothalamic cells *is* satiety. If the VMH is "happy", the brain assumes that the rest of the cells in the body will also be getting enough metabolic substrate to also be "happy".
I laid out in too much detail how linoleate oxidation damages this system during the last post.
Obesity results from a failure of individual cells to adequately signal that they are "full" when they are actually having all of their energetic needs being met. This applies as much in the VMH cells as in those anywhere else with insulin regulated caloric ingress.
None of which excludes the related loss of calories in to adipocytes which will, in its own right, actually reduce the level of metabolic substrate being visualised by the VMH to compound the problem. Another post there.
Also, we need to think about the role of insulin resistance in established obesity. It's still functional but in a very different context.
Peter
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