hello everyone
today i was in bio class, and we discussed different hormones, amongst them there was also insulin, so i had a home game actually. as we were discussing this bg regulation with insulin and glucagon, a student asked if the glucagon is still produced normally in the pancreas of a type one diabetic. the teacher asked me, as he knew i'm diabetic, but i actually couldn't really help them either. the glucagon production doesn't really work in the body of a type one, otherwise we had almost no hypos, right? but to my knowledge the immune system attacks only the beta cells.
so why does that not work properly?
does anyone know?
Glucagon and/or other parts of gluconeogenesis are often disrupted/messed up in diabetics.
Certainly a long string of hypos will totally deplete the liver of glycogen. Then it doesn't matter how much glucagon there is, there will not be any glycogen for the liver to turn into glucose.
Some medicines that some diabetics take, such as metformin, work so well because they PURPOSEFULLY disrupt gluconeogenesis in the liver. This is one of the reasons why for many T2's, a low carb diet plus metformin really is a wonderful combination.
There is indeed some protective value against the worst effects of hypos but the liver has to have glycogen and it seems likely that in the event of a string of hypos the protection will not be there when it counts.
From what I have read, the glucagon production and reaction to lows gets worse over time in type 1, I'm not sure why. This article seems to confirm that.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1021855/
I'm sure if you google enough you can find info on why people think this may happen.
My feeling is that just like hypo awareness problems, over time a lot of repeated hypos will also blunt the natural glycogen response.
But even for a complete non-diabetic, injecting excess insulin results in low bg and sometimes death. Sure, sometimes the glucagon kicks in and saves their life, but they often go into coma/seizures even if they live through the insulin injection:
Murder by insulin: suspected, purported and proven-a review.
Marks V.
Source
University of Surrey, Guildford, UK. vincentmarks@btinternet.com
Abstract
Murder by insulin-whether attempted, suspected or proven-is rare. Only 66 cases worldwide could be found for this review. A conviction was secured in 31 cases and additional weapon was employed in 11. Differentiation of attempted homicide from Munchausen syndrome by proxy in the young and from 'mercy killing' in the elderly was not attempted. Most perpetrators were close relatives and most victims were alive when discovered and responded to treatment. Hypoglycaemia is the first clue to homicidal insulin use in living subjects and requires the demonstration of a plasma insulin concentration of generally more than 1000 pmol/L and undetectable plasma C-peptide concentration to establish the diagnosis. Serum glucose measurements are valueless in victims found dead. The presence near the body of insulin vials, syringes or needles, loose talk by the suspected perpetrator or their ready access to insulin may be the only clue. The demonstration of insulin in tissue around an injection site by immunohistopathology or by measuring it in an extract clinches the diagnosis. Immunoassays suitable for clinical use to detect and measure insulin and C-peptide are subject to random errors and cannot be relied upon unless special precautions including separation by gel filtration or HPLC are undertaken prior to analysis. They do not detect or measure accurately a new generation of synthetic insulin analogues. Mass spectrometry will be required to do this and to validate clinical immunoassays, upon which convictions have always had to rely in the past.
I know! I know! Pick me! :-)
T1 actually attacks the clusters of cells known as the Islets of Langerhans. The islet cells include both alpha and beta cells. Most people think that only the beta cells are affected because the beta cells make insulin, but that isn't true. Admittedly, the attack on the alpha cells seems slower, but that could be because they aren't in use all the time while the beta cells are. The more they need to compensate, the more they're attacked. That's why their ability to work declines more slowly than that of the beta cells.
You're welcome. :-)
Actually, an issue with diabetics is not that we have impaired glucagon production. It's the opposite, really. We have a difficult time suppressing glucagon production even under conditions where it should be suppressed.
We are under the impression that when insulin is being released, glucagon is being suppressed, and vice versa. When we eat, it is generally true that insulin is released while glucagon is suppressed. For diabetics, however, glucagon suppression is impaired. Glucagon secretion is why we have Dawn Phenomenon, respond to stressful situations with huge BG spikes, and can exercise like maniacs and have a BG spike afterwards.
The reason why T1s have hypos is mismatching of our insulin dose (basal and bolus) to the amount of carbs we eat and the amount of circulating glucagon we have. Basically, any time we take insulin, we have to account for the number of carbs and for any circulating glucagon, but we just roll the dosage into one big calculation we call Insulin to carb ratio. Any time we have a hypo, it's because we've taken too much insulin.
thanks Guitarnut :)
I presume the alpha cells are involved in glucagon response and other things? I'm going to go google that one.
I agree I think repeated bad hypos have affects too... I think I had heard of people committing murder with insulin before but had forgotten about it. I knew the friend of someone who was type 1, several years ago he was getting married. All of a sudden he passed away after the marriage and his wife becoming pregnant. We always suspected there was foul play on her part due to the whole circumstances. No proof of course.
yes, this is true and what my endo told me...that's why, as the disease progresses, if one's honeymooning, both alpha and beta cells die off and highs and low become stronger, worse, etc...there's also a huge link with the liver and also amyillin(sp) another hormone we're lacking. that's why type 1 is so different then type 2 diabetes. Potassium plays a huge factor in all this too. It's very complicated, we think we just need to 'take' insulin but it's an entire system (for a type 1) where dual organs and hormones have and are malfunctioning.
isn't the liver doing a dump with this? the role of a basal insulin, per my endo, is to shut off the liver dumps and the release of glycogen (stored sugar), the alpha cells play a role too, not sure how it all works together though.
Interesting explanation... I think some of my hypos have been due to activity and also to the fact that my pancreas is still producing insulin and decided to produce more since they happened when I had no fast acting active and my basal is not too high as far as I know. Also our insulin needs are always changing throughout the day with 3 am being the lowest need usually. according to the article I found type 1 does have a worse glucagon response after 10 years so I wonder if the alpha cell destruction is involved in that? I think the alpha cells do play a role, I'm going to read more about it.
injecting insulin is a very crude method compared to what our pancreas normally does.
I knew about amylin production dropping, but substituting that was making me nauseous and I went low too much- it was very difficult to time. I wonder if more hypos stress out the alpha cells? I think there are many things we don't understand about both types most likely.
Yeah, but the liver dump is under hormonal control and, from what I understand, the hormone is glucagon released from the alpha cells. Other hormones, like adrenalin, can stimulate the release of glucagon as well.
Insulin and glucagon are antagonists. They have opposite actions, for the most part, and the normal production of insulin from the beta cells should suppress glucagon release from the alpha cells. So, if you have basal insulin on board, that should be working to suppress glucagon release. From my previous post, though, this action can be impaired in diabetics.
Taking into account the post by meee, it sounds like glucagon production in diabetics is a big ol' mess, and there aren't any simple answers to what's going on with the overall insulin/glucagon response.
there's glucagon from alpha cells which works in the pancreas and helps regulate hypos which is malfunctioning from the autoimmune attack. the liver stores glycogen, which is released when we're sleeping, etc...and has nothing to do with the pancreas. that's why we need to take a basal insulin regardless if we eat or not. that's why, if our basal isn't correct, our blood sugars will continue to rise without any challenge of food. i believe they're two different things. Isn't this what metformin does for type 2's, because type 2's make insulin and don't have the autoimmune disease their oral med metformin works on surpressing the liver from releasing too much glycogen (stored sugar)?
This makes the most sense of anything I've read about alpha cells. I too have wondered if they were the target of the autoimmune attack or not. Your statement that they are destroyed more slowly perhaps because they are not as "active" as insulin makes sense to me from what I have experienced with lows over the years.
I'm with FHS here. Glucagon works relatively normally in T1, but glucagon as a signal sometimes get's messed up. The normal signal to our livers to release glucose in response to a hypo is increased glucagon and decreased insulin. Except those of us who use insulin, when we take too much insulin we don't have decreased insulin. Insulin suppresses the glucagon signal to our livers and it doesn't release glucose when it should and we have a hypo. It is the counter regulation response that is impaired, not the glucagon secretion.
In my case, as a T2, if I can keep my basal insulin set as just enough I can actually still counterregulate and I don't have to treat a mild hypo.
Glucagon is released from the pancreas, but it doesn't simply remain in the pancreas. All hormones are released into circulation to affect any number of organs far from the site of hormone production. Glucagon is no different.
Yes, glycogen is stored in the liver and is released from the liver but it requires hormonal stimulation from both insulin to cause the uptake of glucose for strorage and stimulation from glucagon to cause the breakdown of glycogen into glucose for release into the blood.
Here's the best single site I know on Glucagon:
http://www.glucagon.com/glucagon.html
Glucagon is generally viewed as a hormone that opposes the action of insulin in peripheral tissues, predominantly the liver, where the insulin:glucagon ratio determines the intricate control of gluconeogenesis and glycogenolysis. The action of glucagon in the liver is complex and involves coordinate regulation of transcription factors and signal transduction networks which converge on regulation of amino acid, lipid and carbohydrate metabolism.
I'm actually not sure what Metaformin does to suppress glucose release from the liver. I know it targets liver cells but I don't know by what action. My guess is that it blocks receptors, which would involve disrupting the action of glucagon. Dunno for sure though.
fat also stores sugar, the concept being that type 2's who are overweight (too much fat) i.e., insulin resistant, when losing the weight (or even type 1's) will do better with blood sugars.
i believe this is incorrect. alpha cells produce glucagon. the liver stores sugar, fat stores sugar, etc...i'm not sure how it all works, my endo explained it to me, we get liver dumps, stored sugar, which is why we, as type 1's also need a basal, to suppress that, it has nothing to do with alpha cell - glucagon release for lows. this is why a type 2 can take metformin (alone), which works on liver. a type 1 MAY benefit with metformin on board, but will always, always need insulin because our pancreas is 'busted'.
http://en.wikipedia.org/wiki/Glycogen
Glycogen is a multibranched polysaccharide that serves as a form of energy storage in animals[2] and fungi. In humans, glycogen is made and stored primarily in the cells of the liver and the muscles, and functions as the secondary long-term energy storage (with the primary energy stores being fats held in adipose tissue).