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In part 5 of this Exclusive Interview, Raghu Mirmira defines ER stress and how to intervene in the development of this condition in a conversation with Diabetes in Control Publisher Steve Freed.
Raghu G. Mirmira, PhD, MD is the director of pediatric research at Indiana University.
Transcript of this video segment:
Freed: And a lot has been said about the role of ER stress in diabetes.
Mirmira: Yeah.
Freed: What is ER stress? Is it a good thing or a bad thing?
Mirmira: So, ER stress is something that really came into vogue I would say, probably about six or seven years ago. Our group at Indiana and a few other groups around the country proposed that when a beta cell is exposed to certain environmental stresses, whether it could be pathogens such as viruses or other inflammatory insults, cells then begin to produce proteins within their cell that become misfolded. And because proteins run through what’s called the endoplasmic reticulum, these misfolded proteins trigger this whole pathway within the beta cells that causes the cells to ultimately die. And so, we now believe that this whole concept of ER stress probably accounts for how beta cells trigger autoimmunity, because they’re starting to produce these proteins in a sense that the immune recognizes as foreign, so that starts autoimmunity. But then this concept that ER stress proceeds means that the cells die, not as a result of autoimmunity but because it’s a sort of self-programmed death. So, ER stress is both a good thing and a bad thing. It’s a good thing because it’s really designed to allow the cell to try to recover while the insult goes away. It’s a bad thing because as we know in type 1 diabetes whatever that insult is doesn’t really seem to go away, and then so the cells are programmed to die. So, what we need to do in studying ER stress is identify the right points in the pathway that we can intervene. Small molecule drugs for example can preserve beta cells. And if we deliver those drugs perhaps early enough we can even prevent the initiation of autoimmunity. So, I think the whole idea of ER stress is a concept that really allows us to begin thinking about how we can begin treating the beta cell rather than the immune system.