http://www.sciencedaily.com/release...51118180538.htm



On the upside--other than the method of delivery--intentionally compromising the gut barrier--this method has the potential to be closer to physiological insulin than injection is, since the liver would get the first chance at clearing insulin that it normally does when insulin comes from the pancreas.

I also wonder what this method of delivery does, if anything, to the probability of an immune response to the insulin being delivered.

Gastroparesis (compromised stomach emptying) would be an obvious issue, and even in people without this issue, I wonder how predictable the rate and timing of insulin delivery would be.

I saw an ad the other day for nasal insulin. It was in a regular magazine and looked legit. Is that a real thing?

Yes, the term "many" here should be quantified as between 5% and 10% of the total, since that's the number of people with diabetes type 1, so up to 2.9 million. Diabetes type 2 does not require insulin shots or otherwise since a primary feature of the disease is hyperinsulinemia. It seems the article was written purposely to make the "discovery" appear 10x bigger than it really is. Nevertheless, it's an important development, there's many drugs that don't make it through the gut intact, if at all, hence the injections and topical applications.

I wonder what "permeation enhancer" refers to. Gluten? That's a pretty good one.

Considering everything that's been explained so far, that is an unlikely conclusion. First, insulin is destroyed in the stomach, therefore physiologically, we're not adapted to oral insulin. Second, oral insulin delivery requires a "permeation enhancer", something we don't normally eat, therefore physiologically, we're not adapted to oral insulin. Third, insulin would reach the liver from a different route than the liver is used to, i.e. from the gut rather than from peripheral bloodstream. It's unlikely that the liver can handle such a reception equally well, or even that this insulin would be equally active in the liver or even peripherally. There's a similar problem with oral testosterone where when it's ingested, if it makes it to the liver, it's degraded and has no physiological effect besides making the liver work harder than otherwise.

Finally, insulin is a life-long treatment for diabetes type 1. For injection, there's lipohypertrophy at local injection sites from the insulin itself. We'll avoid this with oral insulin, but now we'll have to deal with enteric coating and permeation enhancer effects at equal frequency and duration, i.e. several times per day, every day, life-long. No clue how that's gonna go.

For those who develop fatty deposits at injection sites, would this simply manifest itself in the small intestine at the patch adherence site on the intestine wall? Yes, more testing does need to be done to determine whether this could be an issue.

I have to disagree on this point. The pancreas releases insulin into the portal vein, the liver removes the largest portion (ideally at least). Insulin from the gut would also be absorbed into the portal vein, that's why their saying that this would be more physiological. The bit about the sticky stuff in the gut, and the permeability still makes me nervous. I don't know if it would increase permeability to other substances or not, the patch might provide a sort of barrier itself. But then, what's the aftermath? Does the stick stuff get degraded, is the permeability reverse before this is complete? Who knows?

I've heard about the nasal insulin. The question there is--what will the effect be on the nasal passages and the lungs? Both will be exposed to more insulin than is usual. You could wonder the same about the cells of the gut lining itself, there's liable to be a greater concentration of insulin that those cells are exposed to as well.

And that's in fatty tissue, it's a fairly benign form of hyperplasia. In the gut, I'd think possibility of cancer would be the greater concern.

Yeah, I wasn't too sure how the liver receives stuff from the gut compared to insulin from the pancreas. Thanks for the clarification, Teaser. So I guess that's the only reason it appears to be a better route physiologically. The other stuff just makes it look worse. I'm betting this delivery method will be tried with other shorter-term or lower-frequency drugs first. Peptides could be good candidates, especially GHRH peptides like sermorelin for example, which is currently prescribed as injection once daily for various GH deficiency disorders.

Yeah. Incretin hormones normally secreted by the gut would probably be closest to mimicking nature.