Molecular Switch Could Be Key for Type 2s

With tens of millions of American facing life with type 2 diabetes and many millions more at risk of the disease, scientists are scrambling to unravel novel treatments. The latest breakthrough could come from California’s Salk Institute.

Researchers there have focused on two tiny molecules that form a switch regulating glucose production in the liver. “If you control these switches, you can control the production of glucose, which is really at the heart of the problem of type 2 diabetes,” said the Salk Institute’s Marc Montminy.

Montminy’s research has long focused on a genetic switch known as CRTC2. For people with type 2, said Montminy, “the CRTC2 switch is turned on too strongly because the insulin signal is not getting through. As a result, the liver produces too much glucose, and the level of glucose in the bloodstream is too high. Over a period of 10 to 20 years, the abnormal elevation of glucose leads to chronic complications, including heart disease, blindness, and kidney failure.”

Montminy’s new work has identified the molecular mechanism that turns the CRTC2 switch on full blast. When activated by the fasting hormone glucagon, the molecules form a feedback loop that drives the production of blood sugar.

The potential applications are clear. If the CRTC2 switch could be turned off or even turned down, the production of blood sugar in insulin-resistant patients could be slowed. And if the creation of blood glucose were slowed, diabetic symptoms and complications could be reduced.

It sounds very promising, but, as Montminy said, “We obviously have a lot of work to do to find out whether such a strategy might work in humans.”

The research was published in the journal Nature. Along with researchers from the Salk Institute, scientists from Columbia University, the University of California San Diego, and the University of Ottawa contributed to the paper.


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