New molecule found to regulate blood sugar levels independent of insulin

January 10, 2022
New molecule found to regulate blood sugar levels independent of insulin

Scientists at the Salk Institute for Biological Studies (Salk), US, have identified an alternate molecular pathway that regulates blood glucose, which could present a potential new treatment course for diabetes. While insulin is the primary regulator for the disease, a new molecule called FGF1 was seen to restore blood glucose levels of diabetic mice in just two days. Later studies by the scientists at Salk revealed that brain injections of FGF1 could effectively put diabetes into remission for weeks or months.

The mechanism by which FGF1 functions is slightly different than insulin: insulin uses an enzyme called PDE3B to activate a signaling pathway that suppresses lipolysis. The scientists tested FGF1 with a range of enzymes, including PDE3B, and found that it uses a different enzyme instead – PDE4.

[FGF1 and insulin nevertheless share functions such as regulating glucose production in the liver and by suppressing fat breakdown, or lipolysis.]

“This [PDE4] mechanism is basically a second loop, with all the advantages of a parallel pathway,” said postdoctoral researcher Gencer Sancar. “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.

According to Michael Downes, Senior staff scientist at Salk, “The unique ability of FGF1 to induce sustained glucose lowering in insulin-resistant diabetic mice is a promising therapeutic route for diabetic patients. 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.”

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