[mdup]

I remember reading in another HN thread about insulins (too lazy to search it right now) that plenty of prototype insulins have been developed, but most of them could cause nasty diseases, notably cancer. Hence only a low number of well-tested commercial insulins have been pushed to the market. Does someone knowledgeable have more info about those "good" vs. "bad" insulins?

[snewk]

biologically produced insulin starts as a monomeric protein (meaning it only consists of one string of amino acids) called preproinsulin. this amino acid chain must interact with itself to form stabilizing interactions and disulfide bonds.

once these disulfide linkages are created, this insulin precursor undergoes a multi step enzymatic cleavage which cuts off some bits and makes biologically active insulin.

There are many ways to create insulin synthetically, and some of them lead to product contaminated with misfolded proteins. Misfolded proteins may have no effect, but sometimes they can activate the IGF-1 signal pathway which has been associated with cancer. There is also a chance of an autoimmmune reaction to the misfolded insulin, which would also be very bad.

We are exploring a few different methods for our insulin production specifically with this concern in mind.

[ff7c11]

Misfolded proteins also cause Alzheimer's disease. They are the number one reason why cannibalism is bad. If you eat a human brain with misfolded human proteins (prions) it can cause your proteins to misfold. I think.

[snewk]

Yes, misfolded prion proteins(PrPsc) can 'infect' other correctly folded prion proteins(PrPc). Prions are glycoproteins found on the surface of cells, and they affect cell signaling from the exterior of a cell to the interior.

Insulin, on the other hand, is a free floating small molecule not anchored to a cell. Misfolded insulin is not 'infectious' like PrPsc.

The biological role of prions is still not well known, but one reason prion diseases are such a big deal is that prions are resistant to normal biological protein degredation. They are hard buggers to get rid of. Unlike insulin, which has a specific protease enzyme which breaks it down.

[cperciva]

nasty diseases, notably cancer

Insulin-like Growth Factors (IGF) have been implicated in some cancers. As the name suggests, these enzymes are very similar to Insulin -- so every time someone tweaks insulin there's concern that they might end up triggering whatever (as yet poorly understood) metabolic pathway connects IGFs to cancer.