New Study in Experimental Biology and Medicine Shows the Role of Sphingosine Kinase 2 as Therapeutic Target for Diabetes
WASHINGTON, March 21, 2023 (Newswire.com) - A recently published article in Experimental Biology and Medicine (Volume 248, Issue 1, January 2023) provides a mechanism by which Sphingosine kinase 2 (ShK2) impacts Insulin receptor (InsR) trafficking, thereby regulating insulin signaling. The study, led by Dr. Pu Xia, in the Department of Endocrinology and Metabolism at the Zhongshan Hospital and Fudan Institute for Metabolic Diseases of Fudan University (China), describes that inhibition of ShK2 results in attenuation of clathrin mediated endocytosis of InsR.
Disturbed InsR trafficking is associated with impaired insulin signaling and the development of type 2 diabetes (T2D). Sphingosine kinase 2 (SphK2) is a lipid kinase that regulates a variety of cellular processes, including acting as a key regulator of hepatic insulin signaling and glucose homeostasis. However, the specific function of SphK2 in insulin receptor trafficking remained undefined leading to the current study by Aji et al.
This study, led by Dr. Xia, analyzed the role of Sphingosine kinase (SphK2) in regulating insulin receptor trafficking by analyzing Huh7 cells, which is an immortalized cell line derived from male hepatoma tissue, treated with a specific SphK2 small molecule inhibitor or siRNA. Huh7 cells are often used as a substitute for primary hepatocytes. Flow cytometry and immunofluorescence assays were used to investigate the role of SphK2 in insulin receptor trafficking. SphK2 was found to be able to regulate insulin receptor traffic, while SphK1, another isoform of Sphingosine kinase, did not. These findings demonstrate that SphK2 plays an essential function in controlling hepatic insulin signaling by regulating insulin receptor trafficking.
Dr. Steven R. Goodman, Editor-in-Chief of Experimental Biology and Medicine, said, "Xia and colleagues have provided clear insight into the mechanism by which Sphingosine kinase 2 regulates Insulin Receptor endocytosis, and therefore Insulin signaling and glucose homeostasis. In doing so, they identify a new therapeutic target for treatment of Type 2 Diabetes."
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Source: Experimental Biology and Medicine