Posted by Gabrielle on February 09, 2001 at 20:46:16:
In Reply to: regeneration & autoimmune destruction posted by Therese B. on February 08, 2001 at 23:02:41:
Ok. This is what I have found in a pretty good review (Bouwens and Kloeppel, 1996), but things may have changed more recently.
1) Give a few-days-old or an adult rat streptozotocin, you kill the beta cells and there is no regeneration.
2) Give a neonatal rat streptozotocin, the islets partially regenerate.
3) In adult hamsters, recovery from streptozotocin can but does not always occur. This involves islet neogenesis.
4) In NIDDM, there is no evidence of beta-cell neogenesis. In insulin resistance without NIDDM, there is evidence of more beta cell mass (neogenesis or replication of existing islets or inhibition of apoptosis?)
5) In recent onset IDDM, there are conflicting reports of whether neogenesis occurs or not. honeymoon?
6) In long term type 1's, the pancreas can show islets with cells that are immunoreactive for markers of islet precursor cells.
7) Islet neogenesis possibly occurs in human chronic pancreatitis (could be growth factors get released).
I think that the strongest evidence for continuing autoimmunity comes from Sutherland's twin transplants without immune suppression. They all showed selective rejection of the beta cells which could be modulated by the addition of immunosuppression.
In my opinion, the jury is still out on the question of whether significant islet neogenesis occurs in adult humans. Most human tissue does regenerate to some extent. Islets may be different.
Interestingly, some level of reg seems to be constitutively expressed in humans. This level of this protein, known to induce neogenesis in animals (like INGAP), seems the same for diabetics and nondiabetics in a preliminary clinical study in humans.
Christofilis M et al
The idea of testing the beta cells with blood is really only relevant for twin (syngeneic) transplants right now, because we don't yet know how to create new islets from one's own cells. These kinds of tests would always be positive for allografts. Sutherland seems to have done a lot of work on this, and I am sure that they are developing or have developed some good assays to try to assess the proper level of required immunosuppression.