Phytochemical Derivatives as Antidiabetic Agents: effect on glucose disposal in vivo and in vitro models
Supervisor Name
Hilal Zaid
Supervisor Email
hilal.zaid@aaup.edu
University
Arab American University
Research field
Biotechnology
Bio
Dr. Hilal Zaid is a full professor of biochemistry and cell biology at the Arab American University (AAUP), Palestine. He is a member of the higher appointment committee at AAUP. Dr. Zaid received his PhD in Biochemistry and Molecular Biology from the Ben-Gurion University in June 2005 and then was trained as a postdoctoral fellow at the Banting and Best Department of Medical Research, the University of Toronto, Canada. In 2006, he joined the Program in Cell Biology at the Hospital for Sick Children as a postdoctoral fellow until July 2008. He was recruited temporarily to Ben-Gurion University as a research associate. At the beginning of 2009 (until now), he established his own lab of cell biology, biochemistry, and animal units at AAUP and Al-Qasemi Research Center.
Description
Current T2D treatments include drugs that increase insulin secretion (e.g., sulfonylureas), reduce hepatic glucose production and improve insulin sensitivity (metformin), or enhance insulin action through activation of the PPAR-γ nuclear receptor (thiazolidinediones). Newer drug classes such as GLP-1 receptor agonists, DPP-4 inhibitors, and SGLT2 inhibitors have broadened therapeutic options and offer benefits beyond glucose control. However, these drugs possess side effects, such as severe hypoglycemia, idiosyncratic liver cell injury, lactic acidosis, permanent neurological deficit, digestive discomfort, headache, and dizziness. Consequently, there is growing interest in alternative drugs that mimic insulin action with fewer side effects. Medicinal plant-based drugs represent a promising source of bioactive compounds targeting key pathways in glucose homeostasis. A large number of plants used in traditional medicine have now become a part of the modern world health care system. The rational discovery of novel natural drugs is now better feasible than before due to modern techniques for separation, structure elucidation, and screening. However, to our best knowledge, most of the research groups in this field test only the crude extract efficacy of medicinal plants, with limited efforts to isolate and characterize individual compounds or assess their mechanisms of action. Zaid’s lab tested the efficacy of tens of medicinal plant extracts in treating T2D in vitro and in vivo. Moreover, the chemical composition of the effective extracts was detected by GC/MS and reported recently. About 20 compounds (phenols and fatty acid derivatives; detected at Zaid’s lab) were reported elsewhere as potential antidiabetic agents. However, their effects on glucose disposal and GLUT4 remained unexplored. This project aims to address this gap by testing these compounds in complementary systems to determine their capacity to enhance muscle GLUT4 translocation and glucose uptake in vitro and in vivo. We will focus on natural compounds that could stimulate GLUT4 translocation to the PM and thus increase glucose uptake. This project will establish a biological platform to test the antidiabetic potential of natural compounds, regardless of their source. In this project, the two research groups will combine their complementary systems to evaluate the antidiabetic potential of these compounds. Zaid’s lab will use the rat L6-GLUT4myc cell line to assess GLUT4 translocation to the PM. Aguer’s lab will employ primary muscle cells from healthy individuals and patients with T2D to determine whether the compounds previously tested by Zaid's team can enhance glucose uptake in healthy muscle cells and improve insulin sensitivity and glucose uptake in muscle cells from T2D patients, which typically retain the insulin resistance characteristic of their tissue of origin. The effective ingredients will then be tested in vivo in diabetic mice models.