Chair in Molecular and Developmental Biology shared with GB Magazine . “ We have identified a new player in regulating fat lipolysis that will help us understand how energy stores are managed in the body .”
When we eat , energy-rich fats and glucose enter the bloodstream . Insulin normally shuttles these nutrients to cells in muscles and fat tissue , where they are either used immediately or stored for later use . In people with insulin resistance , glucose is not efficiently removed from the blood , and higher lipolysis increases the fatty acid levels . These extra fatty acids accelerate glucose production from the liver , compounding the already high glucose levels . Moreover , fatty acids accumulate in organs , exacerbating the insulin resistance - characteristics of diabetes and obesity . The lab previously showed that injecting FGF1 dramatically lowered blood glucose in mice and that chronic FGF1 treatment relieved insulin resistance . But how it worked remained a mystery .
The team investigated the mechanisms behind these phenomena and how they were linked . First , they showed that FGF1 suppresses lipolysis , as insulin does . Then they showed that FGF1 regulates the production of glucose in the liver , as insulin does . These similarities led the group to wonder if FGF1 and insulin use the same signaling ( communication ) pathways to regulate blood glucose .
It was already known that insulin suppresses lipolysis through PDE3B , an enzyme that initiates a signaling pathway , so the team tested a full array of similar enzymes , with PDE3B at the top of their list . They were surprised to find that FGF1 uses a different pathway - PDE4 . Finding the PDE4 pathway opens new opportunities for drug discovery and basic research focused on high blood glucose ( hyperglycemia ) and insulin resistance .
With recent funding from the Larry L . Hillblom Foundation , Evans and his team will next examine the FGF1 pathway in more detail , explore where the pathway is located in the cell , and test how the pathway functions during different forms of diabetes .
To learn more about the Evans lab and the Salk Institute , please visit : www . salk . edu .
Ron Evans
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