Could you cure type 2 diabetes by flipping a switch?

Imagine that you could flip a light switch and cure diabetes. Thanks to work from scientists Haifeng Ye, Marie Daoud-El Baba, Re-Wang Peng, and Martin Fussenegger, that illuminating analogy may not be that farfetched. This group, publishing June 24, 2011, in the journal Science, has linked light sensitivity to a protein involved in regulating blood glucose.

Light carries energy, and that energy can transfer to molecules and make them move. We’ve got light-reactive proteins in our eyes, for example. One of these is called melanopsin. You may have heard of taking melatonin to regulate a sleep cycle. Melanopsin registers the fading light of the day or brightening light of the dawn to keep our daily rhythms humming along rhythmically. When light strikes melanopsin, the molecule changes shape. This shape change triggers a cascade of changes in nearby molecules, just as one falling domino can trigger a cascade of falling dominoes. In our cells, the dominoes are other molecules. Usually, the point of the cascade is to trigger a response to whatever started it in the first place, which in this case was light.

But what if we took our triggering melanopsin domino and placed it in front of a different set of molecules? Light would still make it change shape and kick off a cascade of reactions. But the different cascade would have a different outcome.

Playing around quite seriously with these possibilities, Fussenegger and colleagues placed their melanopsin domino at the beginning of a cascade that ends with production of a Very Important Protein (VIP) called glucagon-like peptide 1. This molecule with the long name has an equally long resume. Among its many jobs is stimulating release of insulin, the hormone that ushers glucose from the blood into cells. People with type 2 diabetes often don’t have enough glucagon-like peptide 1.

The same applies to mice with type II diabetes. But linking the melanopsin trigger to the cascade of molecules responsible for making glucagon-like peptide 1 changed all that. Researchers placed a few hundred tiny transparent capsules packed with cells containing the melanopsin switch into the abdomens of the mice. Then, they flipped the blue-light switch. The blue light turned on the melanopsin, which then kicked off the VIP-making cascade. The diabetic mice suddenly showed much better control of their blood sugar and had higher insulin levels. Pardon me while I get all sci-geek verklempt. That is cool, cool stuff.

If this light-switch therapy eventually makes its way from mice to people—always a big IF—there seems to be no limit to what could be done with the melanopsin domino. Beyond diabetes, any disease rooted in the failure of a protein production pathway might be a target for a melanopsin kickstart. Thanks to the work of Haifeng Ye, Marie Daoud-El Baba, Re-Wang Peng, and Martin Fussenegger, we someday could be a light switch away from effective therapy for intractable diseases like diabetes.

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