Glucose Transport in Lactation

Abstract

Lactose is the major carbohydrate of human milk and is also the major osmotic constituent of human milk. Therefore, synthesis of lactose is the major determinant of the volume of milk produced by the lactating human mammary gland. Lactose is synthesized from free glucose and UDP-galactose. Thus, glucose transport is required not only across the plasma membrane but also across an intracellular membrane to the compartment of lactose synthesis. The latter requirement is unique to mammary epithelial cells. Historically, based primarily on subcellular fractionation studies, lactose synthesis was thought to occur in Golgi. Yet, the only known glucose transporter isoform expressed in mammary gland is GLUTI, a plasma membrane glucose transporter. We therefore comprehensively studied the possible role of GLUTI as a glucose transporter. We tested the hypothesis that changes in the amount, activity, and subcellular targeting of GLUTI during lactation are consistent with an important role for GLUTI in the regulation of lactation. The experiments described here summarize our recent work in the lactating mouse mammary gland and in mouse mammary epithelial cells in culture. The results demonstrate that GLUTI is targeted to an intracellular compartment. However, studies in mammary epithelial cells in culture demonstrate that this is not a Golgi compartment, but a low-density, exquisitely Brefeldin A-sensitive compartment of Golgi-related vesicles. This raises the possibility that lactose synthesis does not take place in the Golgi proper. The results strongly suggest that GLUTI appears to be important in delivery of substrate to the site of lactose synthesis.