The Very Fine Line

Sorry about the lapse in posts. Harry Potter. I know. Don't judge me.

Sometimes with pharmaceuticals, there is a very fine line between treating a condition and causing a problem. This is especially true for treatments on the cellular level. Recently, Avandia and Actos, drug treatments for type II diabetes, have faced an impending ban by the FDA. They both belong to a class of drugs called thiazolidinediones. Thiazolidinediones act on peroxisome proliferator-activated receptors or PPARs, which, once bound to a ligand such as a thiazolidinedione or a fatty acid, dimerize with another receptor and act as a transcription factor on the DNA. Read the Wikipedia article if you want the mechanics of how exactly they treat diabetes cause i'm not going to summarize it for you. No sir.

These two drugs, when taken over a 26 month period, cause a 1 in 50 chance of heart failure. That, my friends, is not good. They seem to cause fluid retention. With 7 million people taking the US, you can guess that this spells bad news. It seems that the question must be asked: With billions of dollars being funneled into the development, testing, and marketing of a drug, how did something like this just slip by? Okay, big pharma, lets see you smooth this one over.

Sorry you have Diabetes, your SURs must be retarded

This is an article from Nature by Colin G. Nichols about Kir, an inward rectifying potassium channel that plays a huge part in the insulin secretion pathway. With everyone getting so fat, I figure this is handy knowledge for any biologist.


Kir is an inwardly-rectifying potassium channel that is found in pancreatic beta cells, among other places. It is usually open, but when you give into your gluttonous temptations, all the ATP that is made from the glucose in your double fudge chocolate ice cream closes the channel, causing the cell membrane to depolarize, opening calcium channels. The abundance of calcium in the cystol allows vesicles full of yummy insulin to fuse with the cell membrane, killing your sugar high before you can say bob's your uncle. When your sugar high dies a sad, sad death and intercellular ADP concentration increases, the channel opens and insulin is forced to wait in the cell until you stuff your face again.

ATP can bind to sites in the cystolic face of Kir or to the NBFs (nuclear binding folds) of SUR. Both close the slutty Kir channel. SUR is a regulatory transmembrane protein that is linked to the C-terminus of Kir. The whole pore/regulatory complex interacts with a myriad of molecules like magnesium, PIP2, and sulfonylureas.

Of course, for the 20.8 million cads in the US, sulfonylureas are only useful if you have a mutation in your SUR. For everyone else, they get to shoot up with insulin at mealtime.