November 24, 2009

How cholera, gatorade and potential diabetes treatments tie together

I'll be damned. I actually learned something quite interesting, from biochemistry no less. And to make it more bizarre, it ties three seemingly disparate things together - cholera infection, gatorade, and potential diabetes treatments. Most likely, it's interesting to me because it ties into some interesting physiology. In this strange amalgamation, first there is the cholera bacterium Vibrio cholerae. A nasty bug, it can be quite lethal with amazing speed. It is capable of dehydrating and killing a person in less than 24 hours. How? Basically, the bacterium has figured out a way to permanently open up a Chloride channel in one's intestinal cells (a side note, it also happens to be the same chloride channel affected in many Cystic Fibrosis patients). So your intestines starts continuously pumping out chloride. That sounds innocuous, right? Well, the problem is that water always, always runs downhill and always, always follows an osmotic gradient. That means that when separated by a membrane, water tends to equalize on both sides of the membrane such that the solute concentration (in this case chloride) is equal. So in pumping chloride out, it also draws water out of the cells and into your guts. That then passes out of you in a horrible watery effluent. To make it worse, the bacterium also inhibits the influx of sodium into your cells which means more solutes in the lumen of your gut and more water rapidly draining out of you. Enter gatorade. Or several thousand years ago (the exact dates are historically unknown) when a famous Indian physician named Sushruta prescribed drinking water with rock salt and molasses in it for diarrhea. He lead the way for the Florida Gators' drink of Gator-ade. See, your gut has several ways to bring in sodium and thereby water as it follows the concentration gradient. One way is through sodium transporters. The problem is those are inhibited by the Cholera bug. But your gut is clever. It has another way. Glucose (ie, simple sugar) and sodium can hook up together and catch a ride across into the gut that bypasses the other mechanism and cholera doesn't touch this one. So glucose and sodium are able to enter the gut and mitigate the diarrhea. Fast forward a few millenia into the modern era and this same biological concept which can simply and effectively treat an otherwise horribly deadly disease, is also the basis for all those fancy sports drinks. I'm fascinated by the utter subtle simplicity of the treatment of the cholera infection. Drink just water and you're in trouble as it won't get absorbed. But add a bit of sugar and salt, and now you've reduced the mortality from >20% to just 1%. Now THAT'S an effective therapy. But wait, there's more. Pharmaceutical companies are taking further advantage of this concept (this part is real world, not classroom). There's a sodium-glucose transporter in your kidneys that is responsible for the preventing you from literally pissing calories away which wouldn't be too favorable in the old days when food was limited. But in the modern era where calories are overly abundant, it becomes a clever way to take advantage of your urine. The beauty of the approach is that it lowers glucose safely without pushing your metabolism in any other directions like some of the other meds (Avandia anyone? if you're not familiar, just google it). It also spares your pancreas which is crucial to diabetics. My former place of employ worked on one of these inhibitors and it's currently in Phase II clinical trials (BMS has a compound in Phase III). I never worked on it myself but I had some friends who did and I hope it succeeds for their sake. If nothing else, it'd be a good reward for those people who literally collected GALLONS of mouse and rat urine (CSI is so wrong on how labs really work). And while it would be extremely rewarding to prescribe a drug that one helped develop, I'd settle for being able to prescribe something I watched close colleagues develop. Betcha thought it'd be impossible to tie cholera, gatorade and diabetes together.

1 comment:

Danilo Peterson said...

What about type 2 diabetes? Is mild form of cholera actually beneficial (for pouring excess glucose into gut and out via diarrhoea)? Or is converse true, that cholera would pose more serious threat in those with type two? Interesting thought