Insulin-alternative hormone could open new type of diabetes treatment
Insulin is known for regulating blood glucose levels, and issues with its production lead to diabetes. But now, scientists at the Salk Institute have identified another molecular pathway that regulates blood glucose, which could open up a brand new avenue for treating diabetes.
Normally, insulin’s job is to respond to spikes in blood glucose levels, inducing cells to either use or store that energy. But diabetes can set in when the body either can’t produce enough insulin, or it becomes resistant to the hormone. This of course means that insulin is the main focus in treating diabetes – but perhaps there’s another way.
A few years ago, the Salk team discovered that a molecule called FGF1 performed a similar function to insulin, regulating blood glucose levels. A single injection of the hormone into diabetic mice restored their blood glucose to normal levels for more than two days, while later studies found that brain injections of FGF1 could effectively put diabetes into remission for weeks or months.
For the new study, the Salk researchers investigated the mechanism behind FGF1, and whether or not it works the same way as insulin. They found that FGF1 does function like insulin in some ways, such as regulating glucose production in the liver and by suppressing fat breakdown, or lipolysis. But to their surprise, FGF1 was found to work through a completely different molecular pathway.
Insulin uses an enzyme called PDE3B to activate a signaling pathway that suppresses lipolysis. The researchers tested FGF1 with a range of enzymes, including PDE3B, and found that it uses a different one instead – PDE4.
“This mechanism is basically a second loop, with all the advantages of a parallel pathway,” says Gencer Sancar, first author of the study. “In insulin resistance, insulin signaling is impaired. However, with a different signaling cascade, if one is not working, the other can. That way you still have the control of lipolysis and blood glucose regulation.”
This crucial difference could open up a new area of research into alternative diabetes treatments. FGF1 could be modified to improve the activity of PDE4, or other points in the pathway could be targeted, the team says.
“The unique ability of FGF1 to induce sustained glucose lowering in insulin-resistant diabetic mice is a promising therapeutic route for diabetic patients,” says Michael Downes, co-senior author of the study. “We hope that understanding this pathway will lead to better treatments for diabetic patients. Now that we’ve got a new pathway, we can figure out its role in energy homeostasis in the body and how to manipulate it.”
The research was published in the journal Cell Metabolism.
Source: Salk Institute