The enhancement of glucose uptake caused by the collapse of gap junction communication is due to an increase in astrocyte proliferation

We have previously shown that several gap junction uncouplers increase the uptake of glucose In astrocytes. The aim of the present work was to study w hether the Increase In glucose uptake was a consequence of the inhibition o f gap junction communication and the purpose of this effect. Our results sh ow that alpha -glycyrrhetinic acid and endothelin-1 increase the uptake of glucose in highly, but not in poorly, coupled astrocytes. This effect depen ded on connexin 43 levels and was abolished when the inhibition of gap junc tion communication was prevented by tolbutamide or ouabain. The inhibition of gap junctions increased the rate of glucose incorporation into DNA and R NA, which was inhibited by treatment with dehydroepiandrosterone, an inhibi tor of glucose-6-phosphate dehydrogenase, the regulatory enzyme of the pent ose phosphate pathway. The inhibition of gap junctions significantly increa sed astrocyte proliferation, which was counteracted by tolbutamide. These e ffects were not observed in poorly coupled astrocytes expressing tow levels of connexin 43. The increase in astrocyte proliferation caused by gap junc tion inhibition was prevented when either glucose uptake or the pentose pho sphate pathway were inhibited. We conclude that the inhibition of gap junct ion communication induces astrocyte proliferation, resulting in an enhancem ent of glucose uptake and its utilization through the pentose phosphate pat hway to provide ribose-5-phosphate for the synthesis of nucleic acids.