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Extracellular Glucose Depletion as an Indirect Measure of Glucose Uptake in Cells and Tissues Ex Vivo
Published on: April 6, 2022
Silybin and dehydrosilybin decrease glucose uptake by inhibiting GLUT proteins
Tianzuo Zhan1, Margarete Digel, Eva-Maria Küch
1Molecular Cell Biology Laboratory, Internal Medicine IV, University of Heidelberg, Im Neuenheimer Feld 345, D-69120 Heidelberg, Germany.
Journal of Cellular Biochemistry
|February 18, 2011
Summary
Silybin and dehydrosilybin, compounds from milk thistle, inhibit glucose uptake by directly blocking glucose transporters (GLUTs). This glucose transport inhibition may explain their anti-cancer effects.
Area of Science:
- Biochemistry
- Cell Biology
- Pharmacology
Background:
- Silybin, a major flavonoid from Silybum marianum, is recognized for treating liver diseases and associated insulin resistance.
- Previous research primarily focused on silybin's antioxidant properties.
Purpose of the Study:
- To investigate the effects of silybin and its derivative, dehydrosilybin, on glucose uptake.
- To elucidate the mechanism by which these flavonoids affect glucose transport.
Main Methods:
- Utilized 3T3-L1 adipocytes and Chinese Hamster Ovary (CHO) cells to study glucose uptake.
- Assessed insulin signaling, GLUT4 translocation, hexokinase activity, and cell viability.
- Performed kinetic analysis to determine inhibition constants (Ki) for GLUT4-mediated transport.
Main Results:
- Silybin and dehydrosilybin demonstrated dose-dependent inhibition of basal and insulin-stimulated glucose uptake.
- Dehydrosilybin exhibited stronger inhibitory effects than silybin.
- Inhibition was independent of insulin signaling pathways and GLUT4 translocation.
- Flavonoids directly inhibited GLUT4-mediated glucose transport competitively.
- Expression of GLUT4 partially rescued flavonoid-induced reduction in cell viability.
Conclusions:
- Silybin and dehydrosilybin directly inhibit cellular glucose uptake by interacting with GLUT transporters.
- This direct inhibition of glucose transport offers a novel mechanism, potentially explaining the anti-cancer properties of silybin through glucose starvation.
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