Glucose uptake into lymphocytes is accomplished by non-concentrative
glucose carriers of the GLUT family (GLUT1, GLUT3, GLUT4, GLUT6) and/or by the Na+-coupled
glucose carrier SGLT1. The latter accumulates
glucose against
glucose gradients and is still effective at very low extracellular
glucose concentrations. Signaling involved in SGLT1 expression and activity includes
protein kinase A (PKA),
protein kinase C (PKC), serum- and
glucocorticoid-inducible
kinase (SGK1),
AMP-activated kinase (AMPK), and
Janus kinases (JAK2 and JAK3).
Glucose taken up is partially stored as
glycogen. In hypoxic environments, such as in
tumors as well as infected and inflamed tissues, lymphocytes depend on energy production from
glycogen-dependent glycolysis. The lack of SGLT1 may compromise
glycogen storage and thus lymphocyte survival and function in hypoxic tissues. Accordingly, in mice, genetic knockout of sglt1 compromised bacterial clearance following Listeria monocytogenes
infection leading to an invariably lethal course of the disease. Whether the effect was due to the lack of sglt1 in lymphocytes or in other cell types still remains to be determined. Clearly, additional experimental effort is required to define the role of
glucose transport by GLUTs and particularly by SGLT1 for lymphocyte survival and function, as well as orchestration of the host defense against
tumors and
bacterial infections.