Epinephrine, glucagon, insulin "big picture" clarification

[dfgyz230]

I have a couple of big picture questions that have come up when reviewing metabolism and I think they reflect some fundamental issues in my understanding. Sorry I couldn't be more concise.

1. I don't understand the purpose of gluconeogenesis/ glycogenlysis. I see the purpose is to "maintain blood sugar levels" but why does blood sugar need to be maintained? Again, I've read the reason is so that the rbcs and brain have a fuel source since they "use glucose". However, to my knowledge, insulin is the hormone that pushes us down the pathway of glycolysis, which is how we use glucose for ATP synthesis via aerobic or anaerobic glycolysis. I understand rbcs undergo anaerobic glycolysis, but doesn't this still require insulin, which is inhibited by glucagon(the hormone that is initially putting glucose into blood for the rbcs and brain to utilize)? So if we are keeping glucose in the blood via glucagon, how can we use the glucose for energy when insulin is being inhibited?

2. Related question: is glucagon important because if we only had insulin, all glucose would be shunted into liver, fat and muscle, but not into the brain? I read the brain does not respond to insulin, so would this mean a constant insulin presence would deplete all glucose from the blood, leaving none for the brain to use? My modest guess is that the brain can only "grab" glucose from the blood stream, so if it were devoid of glucose, the brain would lack a fuel source. This is just my guess though. I understand the brain not responding to insulin, and thus engaging in aerobic glyc in both fed and fasted states, is closely related to why it needs blood glucose to be maintained but I seem to be missing something because it makes no sense...

This logic doesn't seem to apply to rbcs; as previously stated, rbcs undergo anaerobic glycolysis, and to my knowledge this would require insulin... so I don't understand why glucagon is needed to keep glucose in the blood to nourish rbcs when insulin could just push us down the path toward anaerobic glycolysis for the rbcs... unless insulin depletes the blood glucose and leaves none for the rbcs and brain which is my best guess.

3. It always made sense to me why we feel tired and lethargic if we haven't eaten all day, as fasting leads to glucagon and epinephrine releasing glucose stores instead of pushing glucose down glycolysis for energy usage. So why is epinephrine released during a fight or flight response??? This is a time when we have rapid energy demands, so why are we doing the opposite of glycolysis? why not use insulin? are we freeing glucose from gylcogen via epinephrine, then having insulin surges to utilize this freed glucose?? This is the most confusing part for me. I thought epinephrine and glucagon make sense in the context of fasting or starving, as the brain is prioritized at the expense of muscle (increased glucagon maintains blood glucose for brain while insulin inhibited so diminished aerobic glycolysis in muscle). However, in fight or flight, shouldn't the muscle be prioritized so why not an insulin spike in this scenario??

The only way this makes sense to me is that during fasting, we are not getting glucose from food, so it must be released from storage via glucagon/epinephrine mediated glycogenlysis. BUT then that freed glucose would need to be used via insulin mediated glycolysis. Or we just need to maintain blood sugar (for rbcs and brain) and we are getting energy from lipolysis of fat and catabolism of amino acids (also mediated by epinephrine and glucagon).

Sorry for the wall of text. God help me my head hurts.

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[theonlytycrane]

I have a couple of big picture questions that have come up when reviewing metabolism and I think they reflect some fundamental issues in my understanding. Sorry I couldn't be more concise.

1. I don't understand the purpose of gluconeogenesis/ glycogenlysis. I see the purpose is to "maintain blood sugar levels" but why does blood sugar need to be maintained? Again, I've read the reason is so that the rbcs and brain have a fuel source since they "use glucose". However, to my knowledge, insulin is the hormone that pushes us down the pathway of glycolysis, which is how we use glucose for ATP synthesis via aerobic or anaerobic glycolysis. I understand rbcs undergo anaerobic glycolysis, but doesn't this still require insulin, which is inhibited by glucagon(the hormone that is initially putting glucose into blood for the rbcs and brain to utilize)? So if we are keeping glucose in the blood via glucagon, how can we use the glucose for energy when insulin is being inhibited?

Blood circulates around the body to transport nutrients, wastes, and many other things to the tissues. We always want blood sugar levels to be stable so that tissues can take in sugar if needed (to break it down for energy). If we didn't regulate blood sugar levels, the levels could totally deplete, or overload into a crazy excess. The saying "in moderation" or "happy medium" being good applies here.

2. Related question: is glucagon important because if we only had insulin, all glucose would be shunted into liver, fat and muscle, but not into the brain? I read the brain does not respond to insulin, so would this mean a constant insulin presence would deplete all glucose from the blood, leaving none for the brain to use? My modest guess is that the brain can only "grab" glucose from the blood stream, so if it were devoid of glucose, the brain would lack a fuel source. This is just my guess though. I understand the brain not responding to insulin, and thus engaging in aerobic glyc in both fed and fasted states, is closely related to why it needs blood glucose to be maintained but I seem to be missing something because it makes no sense...

This logic doesn't seem to apply to rbcs; as previously stated, rbcs undergo anaerobic glycolysis, and to my knowledge this would require insulin... so I don't understand why glucagon is needed to keep glucose in the blood to nourish rbcs when insulin could just push us down the path toward anaerobic glycolysis for the rbcs... unless insulin depletes the blood glucose and leaves none for the rbcs and brain which is my best guess.

Insulin and glucagon are antagonistic hormone pairs. Insulin signals to tissues to take in glucose when blood sugar levels are high and glucagon signals for glycogen breakdown and later gluconeogenesis when blood sugar levels are low. It's all about maintaining blood sugar levels within a healthy range as mentioned above. Remember that a lot of different tissues use sugars, not just RBC. And don't forget about the blood-brain barrier!

3. It always made sense to me why we feel tired and lethargic if we haven't eaten all day, as fasting leads to glucagon and epinephrine releasing glucose stores instead of pushing glucose down glycolysis for energy usage. So why is epinephrine released during a fight or flight response??? This is a time when we have rapid energy demands, so why are we doing the opposite of glycolysis? why not use insulin? are we freeing glucose from gylcogen via epinephrine, then having insulin surges to utilize this freed glucose?? This is the most confusing part for me. I thought epinephrine and glucagon make sense in the context of fasting or starving, as the brain is prioritized at the expense of muscle (increased glucagon maintains blood glucose for brain while insulin inhibited so diminished aerobic glycolysis in muscle). However, in fight or flight, shouldn't the muscle be prioritized so why not an insulin spike in this scenario??

The only way this makes sense to me is that during fasting, we are not getting glucose from food, so it must be released from storage via glucagon/epinephrine mediated glycogenlysis. BUT then that freed glucose would need to be used via insulin mediated glycolysis. Or we just need to maintain blood sugar (for rbcs and brain) and we are getting energy from lipolysis of fat and catabolism of amino acids (also mediated by epinephrine and glucagon).

Sorry for the wall of text. God help me my head hurts.

insulin signals for tissues to take in sugar, but we need sugar in the blood stream to be able to do so. epinephrine signals for sugar release to the blood stream to be available for intake by tissues (it all happens so quickly as you feel that adrenaline rush).

 

[kingtal0n]

I have a couple of big picture questions that have come up when reviewing metabolism and I think they reflect some fundamental issues in my understanding. Sorry I couldn't be more concise.

1. I don't understand the purpose of gluconeogenesis/ glycogenlysis. I see the purpose is to "maintain blood sugar levels" but why does blood sugar need to be maintained? Again, I've read the reason is so that the rbcs and brain have a fuel source since they "use glucose". However, to my knowledge, insulin is the hormone that pushes us down the pathway of glycolysis, which is how we use glucose for ATP synthesis via aerobic or anaerobic glycolysis. I understand rbcs undergo anaerobic glycolysis, but doesn't this still require insulin, which is inhibited by glucagon(the hormone that is initially putting glucose into blood for the rbcs and brain to utilize)? So if we are keeping glucose in the blood via glucagon, how can we use the glucose for energy when insulin is being inhibited?

1. RBC do not need insulin to take up glucose. I believe that many types of cells are able to take up glucose without insulin, only insulin-sensitive cells take up much less of it when there is no insulin.
2. Glycolysis means the cell is breaking up the sugar, it does not matter how the sugar got there (insulin/glucagon) the cell does the same thing with it, tries to aerobically burn it if oxygen is available otherwise anaerobic fermentation.
3.insulin/glucagon are blood sugar maintainers, they just maintain a narrow range of concentration in the blood. If the sugar content goes too high, cells will die, and bad things can happen (blindness? amputation?) If sugar goes too low, you can faint, and cells can die, both are bad. So its very important that in one way or the other, you control that blood sugar, if the insulin fails to do this: we resort to diet, training, blood sugar monitoring. If the insulin still works then we just inject it, or something similar to it, to replace it in the person.

2. Related question: is glucagon important because if we only had insulin, all glucose would be shunted into liver, fat and muscle, but not into the brain? I read the brain does not respond to insulin, so would this mean a constant insulin presence would deplete all glucose from the blood, leaving none for the brain to use? My modest guess is that the brain can only "grab" glucose from the blood stream, so if it were devoid of glucose, the brain would lack a fuel source. This is just my guess though. I understand the brain not responding to insulin, and thus engaging in aerobic glyc in both fed and fasted states, is closely related to why it needs blood glucose to be maintained but I seem to be missing something because it makes no sense...

This logic doesn't seem to apply to rbcs; as previously stated, rbcs undergo anaerobic glycolysis, and to my knowledge this would require insulin... so I don't understand why glucagon is needed to keep glucose in the blood to nourish rbcs when insulin could just push us down the path toward anaerobic glycolysis for the rbcs... unless insulin depletes the blood glucose and leaves none for the rbcs and brain which is my best guess.

Glucagon is there to help the blood raise sugar concentration when there is no food/sugar coming in the digestive tract. This is a fasting hormone (sound it out, what does it sound like? Glu-co-gone? Glu-cose-is-gone? Glucosegone?) and when the glucose in the blood falls low, glucagon saves the day by signaling for cells which can respond to release sugar into the blood. Sugar can be made from amino acids, which is why body builders try to prevent from entering this pathway (amino acids that could be used to build muscle are being used to fight low blood sugar instead) when trying to gain actual muscle.

If you inject too much insulin, yes all the glucose will leave the blood and be shuttled into insulin sensitive cells, leaving your body with low blood sugar enough to knock you out. We did an experiment in BIO class where we put a fish into an insulin solution, and he freaked out big time. We had to "save his life" somehow, I think we put him back into regular water but its been quite a while so I dont remember (the fish didnt die, but would have if you left him in the insulin solution)

3. It always made sense to me why we feel tired and lethargic if we haven't eaten all day, as fasting leads to glucagon and epinephrine releasing glucose stores instead of pushing glucose down glycolysis for energy usage. So why is epinephrine released during a fight or flight response??? This is a time when we have rapid energy demands, so why are we doing the opposite of glycolysis? why not use insulin? are we freeing glucose from gylcogen via epinephrine, then having insulin surges to utilize this freed glucose?? This is the most confusing part for me. I thought epinephrine and glucagon make sense in the context of fasting or starving, as the brain is prioritized at the expense of muscle (increased glucagon maintains blood glucose for brain while insulin inhibited so diminished aerobic glycolysis in muscle). However, in fight or flight, shouldn't the muscle be prioritized so why not an insulin spike in this scenario??

The only way this makes sense to me is that during fasting, we are not getting glucose from food, so it must be released from storage via glucagon/epinephrine mediated glycogenlysis. BUT then that freed glucose would need to be used via insulin mediated glycolysis. Or we just need to maintain blood sugar (for rbcs and brain) and we are getting energy from lipolysis of fat and catabolism of amino acids (also mediated by epinephrine and glucagon).

You have stores of sugar hanging around all over. The liver stores some 5% of it's weight in glycogen. I believe there are small stores on the adrenal gland and somewhere else if Iam not mistaken. Also, the body can manufacture glucose from many structures. When signal'd by glucagon, the liver is one of the big donators to the blood for glucose. It will gradually push glucose into the blood while you fast. This is generally how you get through sleep times, fasting and living from liver glycogen. When you wake, glycogen might be nearly empty from the liver (depends on the person, athletes tend to store more for example) but you arn't truly starving yet. If you kept fasting the entire day and into the next day, a whole new set of rules come into play because now the liver is empty, and the body is more in "starvation mode". See, you can have glucagon present and still not be "starvation mode" yet because of all the glucose available in the liver and hanging around various places. Plus if the cells had a meal earlier they are all topped off. You can think of it like a bunch of little gas tanks. Only once all of the gas tanks start to run really low, does the real "starvation mode" begin, then you get cells breaking down all kinds of things (anything they can find) for making glucose, and many will also kick up (begin to produce/signal for proteins involved in fatty acid catabolism) production of fat burning pathways, which may have been only moving very slowly beforehand (cells seem to prefer glucose, and are "lazy" to burn fat). The body can "get good" at burning fats during certain conditions (ex. a popular diet strategy termed "Ketosis") and true diabetics that do not produce their own insulin will follow this pathway (described once in a book as a "wasting away of flesh and bone into urine") unless they get the life giving insulin that allows their cells to take up the sugars.

Epinephrine helps to QUICKLY push whatever sugar the body has available into the blood, so flight muscles can rapidly take it up for anaerobic respiration (sprinting, fleeing from predators). It might be necessary to hold your breath and sprint/swim long distances, which is what anaerobic metabolism is for (resisting the effects of oxygen debt). This causes glucose to eventually become -> lactic acid which is what causes the burning sensation, in general, for tired muscles and in your liver, that you just used in flight to sprint or heavy/max lifting. If the body didn't have a mechanism to dump sugar into the blood when you got scared, you would quickly sap the remaining sugar trying to flee, and be food for a hungry predator.

Epinephrine also causes a cascade of other reactions which facilitate/assist in high energy metabolism, like opening the air ways for you to breath better (thus it is used to combat allergic reactions which contrict airways) and I am sure a host of other effects you can look up I am sure.