Super interesting article! Would be really interested to see how this connects with the sport science research on lactate for endurance athletes. In elite cycling managing and training lactate usage is a really key focus, and likewise for pw diabetes excercise seems to have very positive effects (although granted basically everyone gets a lot of benefits from excercise).
What predictions does the lactate shuttle model make? Surprising this is still up in the air 40 years later! It does feel like there’s a general trend of “useless” stuff being found to have an important purpose in biology.
I think the simplest prediction would be that in a resting organism with plenty of glucose and in a normal oxygen environment, disabling lactate production should be severely detrimental for most of its organ systems. The "lactate as waste" model would predict that lacking lactate shouldn't be a big problem when there's enough oxygen and not a big oxygen demand.
I _think_ there's a typo in footnote 1? In "Your pancreas secretes glucagon. This prompts your liver and muscles to convert their glucagon" the second glucagon should be glycogen?
A thought: metformin in higher doses or lowered clearance can lead to lactic acidosis - I don't know to what degree lactic acid metabolism is affected within the therapeutic window and if it's casual to metformin antidiabetic effect, anyways seems like a good place to start testing your hypothesis?
Super interesting article! Would be really interested to see how this connects with the sport science research on lactate for endurance athletes. In elite cycling managing and training lactate usage is a really key focus, and likewise for pw diabetes excercise seems to have very positive effects (although granted basically everyone gets a lot of benefits from excercise).
What predictions does the lactate shuttle model make? Surprising this is still up in the air 40 years later! It does feel like there’s a general trend of “useless” stuff being found to have an important purpose in biology.
I think the simplest prediction would be that in a resting organism with plenty of glucose and in a normal oxygen environment, disabling lactate production should be severely detrimental for most of its organ systems. The "lactate as waste" model would predict that lacking lactate shouldn't be a big problem when there's enough oxygen and not a big oxygen demand.
I _think_ there's a typo in footnote 1? In "Your pancreas secretes glucagon. This prompts your liver and muscles to convert their glucagon" the second glucagon should be glycogen?
Fixed, thanks. It's so annoying how similar glucagon and glycogen are as words lol.
Great summary!
A thought: metformin in higher doses or lowered clearance can lead to lactic acidosis - I don't know to what degree lactic acid metabolism is affected within the therapeutic window and if it's casual to metformin antidiabetic effect, anyways seems like a good place to start testing your hypothesis?