Glut-1 expression and its response to hypoglycemia in the embryonic mouse heart.

Abstract

The embryonic heart depends on glucose during early organogenesis. Glut-1 functions in constitutive glucose uptake in adult tissues and is the predominant glucose transporter in embryonic and fetal tissues. This study focuses on Glut-1 expression in the heart during normal organogenesis using immunohistochemistry for Glut-1 distribution, Western analysis for Glut-1 protein levels, and reverse transcriptase polymerase chain reaction for Glut-1 mRNA levels. The role of Glut in glucose uptake response to hypoglycemia in the embryonic heart is evaluated using the Glut inhibitor cytochalasin B. Cardiac Glut-1 expression is also evaluated after in vitro hypoglycemic exposure. Glut-1 levels are highest on gestational days 9-10, intermediate on gestational day 10.5, and lowest on gestational days 11.5-13.5 in the normal embryonic heart. Cardiac Glut-1 mRNA levels similarly decline between gestational days 9.5 and gd 13.5. Cytochalasin B produces a dose-dependent decrease in glucose uptake in hearts exposed to hypoglycemia for 30 min or 6 h, implicating Glut in this response. Glut-1 protein expression is unchanged after 2 or 6 h but increased after 12 and 24 h of hypoglycemia in the gestational day 9.5 heart. Thus, Glut-1 expression is prominent in the embryonic heart and is correlated with changes in cardiac glucose requirements during normal organogenesis. Glut activity increases in response to acute hypoglycemia and the expression of Glut-1 increases in response to prolonged hypoglycemia. These results support the importance of Glut-1 during normal cardiogenesis and in response to hypoglycemia in the embryonic heart.