Glucagon and insulin release

[Zzmed]

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Guys,

FA says that glucagon stimulates insulin release and further glucagon release.

Can someone elaborate on this?
I mean, i get the first one, that glucagon needs insulin in order to utilize the newly formed glucose from glycogenolysis and gluconeogenesis. And that insulin is needed in case you get hyperglycemic.
BUT i don't get the fact that glucagon induces further glucagon release. It only makes sense to me if it follows insulin release: Glucagon stimulates insulin release ---> glucose into tissues etc etc---> hypoglycemia---> glucagon release.

Any thoughts?

 

[Phloston]

Firstly, insulin inhibits glucagon release. It doesn't stimulate it. Even if you've conjured some indirect mechanism through which insulin lowers sugar levels, thereby necessitating glucagon release, if you're ever asked about insulin's effects on glucagon: insulin inhibits glucagon release. I've seen that in numerous practice questions and that's HY.

Secondly, glucagon acts via G-alpha-s on beta-cells (as does epinephrine), so it increases cAMP, thereby activating PKA, thereby increasing the ATP/ADP, leading to closure of the ATP-gated K+ channel --> depolarization of beta cell --> Ca2+ enters --> insulin release. So in short, whereas insulin inhibits glucagon release, glucagon stimulates insulin release.

The ATP/ADP also increases when glucose enters the beta-cell via GLUT2. However, when glucose is high, cAMP is low (to that effect, remember that high glucose is always associated with low cAMP levels; this also applies notably to the lac operon), which is purposeful because an increased ATP/ADP induced via glucose directly obviates the need for a cAMP-induced augmentation of the ratio.

I've never heard of glucagon inducing further glucagon release. Since glucagon increases intracellular cAMP, that would mean that glucagon release itself is cAMP regulated, but that wouldn't make sense because high glucose levels are associated with low cAMP, and we'd expect high, not low, glucose levels concurrent to glucagon release. So I would argue against glucagon stimulating its own release (which source did you read that?).

 

[Zzmed]

Firstly, insulin inhibits glucagon release. It doesn't stimulate it. Even if you've conjured some indirect mechanism through which insulin lowers sugar levels, thereby necessitating glucagon release, if you're ever asked about insulin's effects on glucagon: insulin inhibits glucagon release. I've seen that in numerous practice questions and that's HY.

Secondly, glucagon acts via G-alpha-s on beta-cells (as does epinephrine), so it increases cAMP, thereby activating PKA, thereby increasing the ATP/ADP, leading to closure of the ATP-gated K+ channel --> depolarization of beta cell --> Ca2+ enters --> insulin release. So in short, whereas insulin inhibits glucagon release, glucagon stimulates insulin release.

The ATP/ADP also increases when glucose enters the beta-cell via GLUT2. However, when glucose is high, cAMP is low (to that effect, remember that high glucose is always associated with low cAMP levels; this also applies notably to the lac operon), which is purposeful because an increased ATP/ADP induced via glucose directly obviates the need for a cAMP-induced augmentation of the ratio.

I've never heard of glucagon inducing further glucagon release. Since glucagon increases intracellular cAMP, that would mean that glucagon release itself is cAMP regulated, but that wouldn't make sense because high glucose levels are associated with low cAMP, and we'd expect high, not low, glucose levels concurrent to glucagon release. So I would argue against glucagon stimulating its own release (which source did you read that?).

I am trying to get a good grasp of the sentence in pg 316 in FA 2012.
"Stimulation of insulin and further glucagon release"

I didn't say that insulin stimulates glucagon release directly. But indirectly. Insulin--> hypoglycemia--> glucagon. (Not normally, but think of cases like postprandial hypoglycemia etc).

And of course glucagon stimulates insulin release since it increases cAMP levels.

As you mention, there is no way glucagon stimulating its own release so i gave the explanation above...

 

[Phloston]

I am trying to get a good grasp of the sentence in pg 316 in FA 2012.
"Stimulation of insulin and further glucagon release"

I didn't say that insulin stimulates glucagon release directly. But indirectly. Insulin--> hypoglycemia--> glucagon. (Not normally, but think of cases like postprandial hypoglycemia etc).

And of course glucagon stimulates insulin release since it increases cAMP levels.

As you mention, there is no way glucagon stimulating its own release so i gave the explanation above...

For the bold statement above, I actually have in my FA, per the FA errata, that point #3 should read as: "increases insulin release and further glucagon release." (which is pretty much what you've just said, but I'm just being technical bc that's what the errata says)

My interpretation of this is: "glucagon increases insulin release directly, the latter of which in turn can lead to further glucagon release."

 

[Zzmed]

My interpretation of this is: "glucagon increases insulin release directly, the latter of which in turn can lead to further glucagon release."

Exactly! This is what i've said from the beginning.
Thanks for the tech...