So why not just insulinate all our strokes and cardiac
arrests? Certainly, your lab and others have accumulated evidence that insulin
(and other growth factors) are salutary in the setting of brain ischemia.
Moreover, insulin is cheap, available and familiar to physicians. What are we
Here's the problem with insulin in brain ischemia: it
doesn't work. (You may start to detect a pattern here.) At least not yet, and probably not by itself. There are some problems with deploying insulin
in the clinical arena at this juncture.
For all that, there's an even more important reason why insulin is
unlikely to be a panacea in the setting of global brain ischemia.
- The dose. In our studies on protein synthesis, Akt activation
and cytochrome c release, we've found that huge doses of insulin are
required--up to 20U/kg. That's about, oh, a zillion times the usual dose.
Obviously, there is a huge potential for problems with hypoglycemia, hypokalemia,
and other metabolic derangements with a dose this large.
- Window of opportunity. Our default mode is to believe that
treatment should begin earlier rather than later. Certainly, this is true when
it comes to apoptosis. But when is the best time to turn on protein synthesis?
As we noted earlier, there is some uncertainty about this.
- Conflicting evidence. It's only fair to tell you that there
is some evidence that insulin can actually worsen outcome in focal ischemic
stroke. This evidence is limited and flawed, but cannot be ignored.
- No clinical evidence. Until insulin is studied in humans,
it's not ready for prime time.