Humans vs. Naked Mole Rats

Blood Sugar, Insulin, Superoxide, Couch Potatoes

(Thanks to my loyal readers for the inspiration for this article.)
There is a lot to be learned by sticking one's head in the sand.  Mole rats of East African deserts are just as naked as humans, but beyond the lack of hair and complex social structures, we are as different as night and day.  These differences explain some of our unusual physiological characteristics.  Maybe our health problems are linked to our sweaty skin, predatory nature and our need to run, just as the naked mole rats (NMRs) are adapted to their dark, high carb, climate-controlled burrows.

Mole Rats:

• low metabolic rate controlled by eating
• live in low oxygen burrows
• poor temperature regulation
• live in the tubers that they eat -- sweet potatoes with legs
• no insulin or superoxide dismutase
• vitamin C and D production (in darkness)?
• no pain sensors in skin, no stress, no sweat
  
• mostly vegetarian, starch

Humans:

• high metabolic rate controlled by physical activity
• live in high oxygen
• temperature regulation by sweating
• hunters, runners, farmers
• no vitamin C production, vitamin D via sunlight
• insulin used to regulate blood sugar, insulin resistance by superoxide
• oxidative stress leads to inflammation and disease
• carnivores, fat

Naked Mole Rats Are as Unique as Humans

Naked mole rats and humans are odd compared to most mammals.  Those oddities may explain a lot about modern human diseases.  The biggest difference between humans and NMRs is the control of blood glucose.  It seems that NMRs control their metabolism by their eating.  In times of starvation, the NMRs eat less and their metabolic rate lowers.  At the cellular level, this must mean that fat stores are converted to blood glucose to modestly regulate blood sugar as it drops, but the lack of insulin does not permit control of high blood sugar.  Thus, a rise in blood sugar must lead to cessation of eating.  This would make sense, because NMRs husband their resources -- they typically encounter few, very large, starchy, underground tubers/roots, eat into them and continue to live off of them for their lifetimes.  They are underground farmers.  They do not wolf down their slow moving prey and hunt for more.

NMRs Know When to Stop

Individual cells of NMRs regulate their metabolism without apparent recourse to adjusting their surface glucose transporters, since their blood glucose levels are constant or unmanipulateably low.  There is no mechanism for blocking influx of glucose by insulin stimulation when intracellular glucose is too high.  It would be expected that intravenous injection of excess glucose could kill NMRs by producing excess intracellular glucose spilling excess high energy electrons of the electron transport chain into superoxide damage.  Of course low tissue oxygen levels would provide protection, since the rate of superoxide formation is proportional to oxygen concentration at the mitochondrial surface.

Humans Are Runners

Humans are adapted to running down prey during the heat of the day, which means that they produce high metabolic rates, high demands for cooling, high tissue oxygen levels and high glucose/fat utilization.  In a lengthy chase, glycogen is rapidly depleted and fat metabolism ensues.  Human brains are adapted for access to lots of oxygen and nutrients.  Human tissues are adapted to low serum glucose and high levels of oxygen.  Moderate levels of serum glucose lead to increased cellular metabolism via insulin production and increased glucose transport into cells.  Low serum glucose leads to lipid mobilization and liver gluconeogenesis.

Humans Kill for Fat

Physical activity regulates human cellular activity.  Depletion of celllular ATP leads to an increase in cell surface glucose transporters.  Inadequate serum glucose, low intracellular glucose (phosphates) and low ATP lead to lipid utilization.  Lipids are all metabolized in mitochondria and require oxygen as the last, low energy electron acceptor in the electron transport chain.  Brain evolution in humans was adapted to high metabolism and intelligence is associated with intense brain vascularization, oxygen supply and lipid utilization.  It could be argued that glycogen storage is a way for humans to handle excess blood sugar during sleep inactivity, since humans are adapted for handling fats and tolerating carbohydrates.

Sweet Tooth Is Deciduous

Why do humans have a sweet tooth?  A group of early humanoids stumbling onto a cache of cookies made by elves, would quickly eat themselves into a stupor as their blood was diverted from brain to belly, their blood sugar rocketed, insulin surged, glucose gushed into cells, cellular metabolism peaked, cellular ATP pegged over, and superoxide spilled high energy electrons out of the saturated mitochondrial ETC.  Cookies would be killers for humans, if superoxide production didn’t block insulin-based transport of glucose into most cells and channel the high blood glucose into fat deposition. 

Marauding Naked Mole Rats

Cookie-fed humans become fat, lethargic and start to look like potatoes with legs, i.e. NMRs.  Unfortunately, unlike NMRs, humans don’t have off switches for carb glutting.  Humans evolved to run on fats, and can exploit occasional carb caches, because of an adaptive sweet tooth, but lack of evolutionary experience with gigantic carb caches, e.g. agriculture and supermarket cereal aisles, left humans maladapted for high carb diets.  We can’t pull out the HFCS intravenous line and instead become couch potatoes waiting as potential victims for giant marauding NMRs (the healthcare industry).  Fortunately, NMRs can keep the potatoes fat and feed on them indefinitely.