the random musings not worthy of new thread thread

[Susquehanna Birder]

And it's intended for Type II.

[reese125]

MMH--whats the scoop with the pill vs the inhaler?

it seems as though the problem with the pill has been that the insulin is gets broken down to quick before it gets to the bloodstream. how have you guys changed that?

The inhaler had a lot of health related issues.  Insulin is a growth factor, and people using the inhaler saw hyperplasia (increased cellularity) of the lungs, which made breathing difficult.
One advantage to oral insulin is that the delivery system is the same as the natural one (dumped into the portal vein as it enters the liver).  The thinking is that most of the insulin will go to the organ where it works, and prevent the high plasma levels of insulin you see with injections, hopefully leading to fewer hypoglycemic shock cases.

It wouldn't completely replace the needles.  Ideally, you'd take a pill with each meal, and a shot at bedtime to get you through the night.

thank you sir.

[MMH]

And it's intended for Type II.

Type II is a bigger market share, which is why they're going after it.  Type I is what it was designed for.  It is just regular fast-acting insulin, delivered orally.

I'd be shocked if they were able to get people to switch from Glucophage (about $5/month, with almost no side effects) to oral insulin, which will be expensive as all hell.  The cost of good will likely be obscene.
Oral bioavailability will still probably only be at best 15%, meaning that the other 85% is essentially waste.  That's a lot of recombinant protein.

Oh, and to answer your original question.  The insulin is chemically conjugated to a short polymer, which is cleaved off in the blood stream.  This polymer makes the protein more fat soluble, and improves it's absorption across the intestine.  The conjugated protein is put in an enteric coated capsule to protect it in the stomach, and I presume formulated to protect it from enzymes in the intestine.  That part came after my time at Nobex.

[Yeti]

I had  a dream last night that I was walking through a field and I found an old cellar door that lead me inside the internet.  It was like a run down city neighborhood in India with all the wire clusters and run down buildings, but up high above all this were beautiful billboards with websites on them.  The internet city smelled like old cinnamon, copper pipes and bad Hoyda .

[reese125]

I always wondered what it would be like to live in my treehouse when I was little, now I know from the tales of Yeti that it wouldnt be all that exciting...actually pretty scary.

Thanks Yeti.

[rjs246]

And it's intended for Type II.

Type II is a bigger market share, which is why they're going after it.  Type I is what it was designed for.  It is just regular fast-acting insulin, delivered orally.

I'd be shocked if they were able to get people to switch from Glucophage (about $5/month, with almost no side effects) to oral insulin, which will be expensive as all hell.  The cost of good will likely be obscene.
Oral bioavailability will still probably only be at best 15%, meaning that the other 85% is essentially waste.  That's a lot of recombinant protein.

Oh, and to answer your original question.  The insulin is chemically conjugated to a short polymer, which is cleaved off in the blood stream.  This polymer makes the protein more fat soluble, and improves it's absorption across the intestine.  The conjugated protein is put in an enteric coated capsule to protect it in the stomach, and I presume formulated to protect it from enzymes in the intestine.  That part came after my time at Nobex.

This is huge news and you are delivering it like a pro. You deserve better than posting on this farging web site.

[Eagaholic]

And it's intended for Type II.

Type II is a bigger market share, which is why they're going after it.  Type I is what it was designed for.  It is just regular fast-acting insulin, delivered orally.

Interesting stuff MMH, but there's a couple of things I don't get.

How could the pill be used as a fast acting insulin for type 1 diabetes (injectable insulin dependent)? With type 1 the dose is determined by finger stick blood sugar readings and needs to be very precise. The dose can vary a good bit throughout the day as well. How can a pill adjust to whatever dose is indicated (unless one may have to take anywhere from maybe 2 to 14 pills at a time depending on the reading)?

Another question is how fast could it work? Regular fast acting insulin starts working quickly, maybe 15-30 minutes. But an enteric coated pill would have to wait to clear the stomach and be broken down and absorbed through the intestine. That takes a good bit more time and is not so predictable.

[MMH]

Good questions.  The idea is to have the insulin be absorbed with the meal as eaten.  This mimics the natural release of insulin when food is detected in the gut.  The absorbed insulin goes to the liver and keeps the glucose spike from the meal to normal levels.  That's why we didn't use the longer acting insulins.  The goal is really to mimic normal insulin release patterns.

Finger sticks would still be required to monitor blood glucose, and if those numbers were off you'd need to take a shot of insulin.

As for speed, the primary absorption site was the upper intestinal tract.  Experiments I ran saw efficacious blood levels within 30 mins.

[Susquehanna Birder]

On the other side of the Type I coin, there are some pretty big advancements in trying to mimic the function of the pancreas (well, as far as the islet cells are concerned). My kid has been participating in trials (as a subject, not a researcher) for the continuous glucose monitoring system (CGM) that communicates directly with her insulin pump. Pretty amazing technology. There are still a few bugs, but we're getting close to a real, closed-loop type of system.

[SD]

Fat black chicks fighting fat white chicks in the middle of the street during NBA All Star weekend:
http://www.youtube.com/watch?v=nPtleQsBn-A&feature=youtube_gdata_player&has_verified=1&oref=http%3A%2F%2Fwww.youtube.com%2Fverify_age%3Fnext_url%3Dhttp%253A%2F%2Fwww.youtube.com%2Fwatch%253Fv%253DnPtleQsBn-A%2526feature%253Dyoutube_gdata_player

Possibly the greatest thing ever posted on this board

[Sgt PSN]

Dude slapped her fat ass.  Hilarious

[phattymatty]

i'd like to say i would have stopped that but there is zero chance i would have.

[mussa]

what a train wreck. you don't stop that you watch and laugh.

[DH]

call me crazy but i dont enjoy watching chicks duke it out like that..id much rather watch a couple of dudes who know what theyre doing go to town on each other

[Diomedes]

Outside of boxing or MMA, etc., I don't like watching people fight at all.