This video is quite interesting regarding glucagon's role in the pathology of diabetes, and suppressing glucagon without insulin in the treatment of diabetes - even type I.


http://youtu.be/VjQkqFSdDOc

Very interesting information about role of glucagon in diabetes. I'm wondering as a T2 diabetic how to apply this information. Are there ways to lower glucagon naturally without glucagon suppressants (not available to me)? Is low carb beneficial for this? Am I correctly understanding that he's saying too much fat in the pancreas causes these problems? Would weight loss if I could find a way to do it help? Low carb, ketosis and exercise just don't seem to help me lose weight like all those cool success stories I read about, so still trying to figure out if there's anything short of unsustainable constant under-eating and hunger that would.

Undereating or fasting does seem to work pretty consistently. Problem is, eventually you have to eat, and the resulting increase in appetite from the extreme dieting leads to 'overeating.' There's an increased risk of type II diabetes in children/animals who are growth deprived through undernutrition, maybe that's due to "overeating" during catch-up growth.

Most people can do what it takes to lose weight, it's maintenance that gives trouble. If calorie restriction, whether through appetite suppression from a diet change, or fasting, or the bare-knuckled type, decreased pancreas fat and reversed diabetes--maybe then the problem could be looked at differently, as how to refeed in such a way that it doesn't cause a refattening of the pancreas and liver?

Another thing--there's the clashing paradigms of very low fat vegan vs. very low carb vs. diabetes. Both seem to have evidence in their favour.

Gary Taubes even wrote about studies showing an increase in insulin sensitivity when people were given very high carbohydrate, low fat diets. He suggested as a possible explanation that on very high carb intake, the adipose tissue might retain its insulin sensitivity longer than otherwise--so the increased insulin sensitivity might be happening at the expense of increased fat storage. But... glucose-lipid toxicity seems to require both an excess of free fatty acids, and an excess of glucose, one or the other won't do. On a very high carbohydrate diet, free fatty acids will be more strongly suppressed. On a low carb diet, glucose is scarce. Sort of the opposite of between a rock and a hard place, between two havens.

I like the way Professor Unger widens the insulin hypothesis of obesity. It isn't dietary carbohydrate drives insulin drives obesity--it's glucose, endogenous or exogenous, drives insulin drives obesity. It makes sense of how people who are particularly sensitive to dietary carbohydrate might be more sensitive to glucocorticoid, glucagon, maybe even growth hormone driving glucose up and thus driving insulin up.

One interesting thing in longevity research--growth hormone deficiency leading to increased lifespan is a common finding. This usually comes with a lower respiratory quotient--lower fasted glucose vs fat oxidation. Insulin was an early target for longevity, doesn't seem to quite fit. Glucagon? Gotta wonder if it would be a suitable target for longevity.

Wow... interesting! So suppressing glucagon is important to controlling diabetes. Fascinating! Seems like this could lead to better diabetic control, if it gets past the dogmatic folks.

Bookmarked to come watch video and then come back wehn I have time.

Very interesting video. Thanks for finding it RawNut.

And another "Wow" from me!
This is the best and most surprising article I've seen/read in months. Light potentially shone on so many loose ends.

I will post the link to the paper for ref. Professor Roger Unger http://www.jci.org/articles/view/60016 .
It is a bit unsettling that it's more than three years since the JCI paper above was published and it has not yet illuminated the academic/medical (or at least blogging) heavens.

Like many "new dawns" the next step will be to see how well it withstands critical review, especially by disinterested parties I respect. I'm thinking Peter "Hyperlipid" at http://high-fat-nutrition.blogspot.ie/ for one. I'm off now to search for such. Will post anything significant I find.

I've been thinking about these questions as well. I'm not diabetic but borderline pre-diabetic and trying to curtail the disease at this point.

I don't know if you are familiar with the intensivedietarymanagement.com site. Dr Fung is a Canadian nephrologist who is putting diabetics in remission with a combo of low carb and fasting. In this lecture , originally delivered as part of Grand Rounds at his hospital, he talks about the vicious cycle of diabetes, obesity, fatty liver, and if I remember correctly, fatty pancreas as well. He is someone else I expect to address Unger's findings as he seems interested in delving deeper and deeper and does not seem to mind learning new information which challenges his beliefs.

In one of his slides, it says "insulin is not essential to life". When insulin receptors shut down in the pathology of diabetes type 2, we get sick. The implication is that insulin is essential for life. I'd like to see some research into insulin deficiency vs growth, longevity, and all those things which keep us alive and well. Simply suppressing glucagon in mice doesn't cut it.

I doubt that any practical application of this idea would involve suppressing glucagon to the point where no insulin at all would be needed. Or maybe I just doubt that it should. Who knows what people are likely to get up to? Pilot studies have already shown that use of leptin, which also helps regulate glucagon, along with insulin, gives better blood glucose control to fragile diabetics. Better blood glucose, less risk of hypo. Suppressing glucagon with something other than insulin allows for a sort of different application of Dr. Bernstein's "law of small numbers."

Good points, though. I'd like to see some lifelong studies with insulin-free mice. The longest-living rodent is pretty much the naked mole rat, their fasted insulin is so low it's been described as unmeasurable.

I'd rather have the option of a way to suppress glucagon, rather than chase hyperinsulinemia with yet more insulin, though. I don't know if it would be "normal," but it feels like it might be closer to normal.

It's entirely possible that most of what insulin does comes about by suppressing the effects of glucagon, so with the lack of insulin paired with lack of glucagon, there might not be such a lack of the "usual actions of insulin" as you'd suppose. Anybody eating a ketogenic diet is hoping for normal function at very low levels of insulin.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3028337/









I've always found this bit interesting--that the "lipostat" hormone that's supposed to control body fat can also control blood glucose and thus insulin.



I wonder from this what the fasting tolerance is like in these animals. Maybe reactive hypoglycemia isn't an issue.

I could've sworn he has a number of mice that produce no insulin, proving that it isn't necessary. At least, not in mice and (dogs, I think).

quick read
http://www.livestrong.com/article/1...mylin-diabetes/

http://www.ncbi.nlm.nih.gov/pubmed/18458326



This maybe fits in with Squarecube's article about amylin as a glucagon suppressor. Glucagon drives blood glucose drives insulin, drives fat gain (and possibly leptin resistance). Suppress glucagon, suppress obesity? With or without diabetes.

But then there's this;



Not that amylin is bad, I guess. Not needing too much of it, so it's not overproduced (or over-injected) to help control blood glucose seems like a good idea.

http://www.ucdmc.ucdavis.edu/publish/news/newsroom/6266

Another connection between blood glucose and Alzheimer's. The red--does that mean damaged amylin is being released from the beta cells? If the oligomerization is happening there, and not in the organs it ends up accumulating in, I guess that could be good news for injected amylin.

Bad amylin=hyperglycemia=need for amylin=more bad amylin....





http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3818462/

I just came across this study;



Cliff notes; insulin degrading enzyme is a target to lower blood glucose in diabetes; keep insulin high by blocking the enzyme, blood glucose should be lower. Turns out the enzyme that degrades insulin also degrades glucagon and amylin. So the effect of blocking the enzyme depends on the ratio of glucagon to insulin. If the glucagon to insulin ratio is high enough--block the enzyme, and most of what it would have been doing is taking down glucagon, so glucagon stays high, and so does blood glucose. When insulin is dominant, as here



then it's primarily the degradation of insulin that's being blocked, so glucose goes down.

Sort of an elegance suggested here, where when things are in balance, the same enzyme degrading hypoglycemic and hyperglycemic-promoting hormones might help keep things balanced--help the system find a lower level of glucagon and insulin while maintaining normal blood glucose, free fatty acids, etc.

http://www.ncbi.nlm.nih.gov/pubmed/24847884

I found this interesting as well (was wondering what other hormones "insulin" degrading enzymes might work on, like leptin.) I don't know if it degrades leptin but there is a relation.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3560472/



Aβ is the amyloid plaque that accumulates in the brains of people with Alzheimer's.