Butyrate regulates glycosylation of the glycoprotein hormone alpha subunit secreted by "glucose-starved" human liver cells.

The alpha-subunit secreted by Chang human liver cells was labeled in vitro with [35S]Met, [3H]GlcN, or [3H]Fuc, and the biosynthetic products were studied by SDS-PAGE. Cells labeled with [35S]Met secreted a homogeneous 23K-24K alpha. In contrast, alpha secreted from cells labeled with [3H]GlcN and [3H]Fuc in the absence of glucose ("glucose-starved") was heterogeneous. This size heterogeneity was altered by glucose and by butyrate, but was little affected by dibutyryl adenosine 3', 5'-monophosphate. In the presence of 0.56 mM (10 mg/dl) or 5.6 mM (100 mg/dl) glucose, or 2 mM butyrate, primarily the larger and presumably more highly glycosylated 24K-25K alpha was secreted. Moreover, the effect of 2 mM butyrate on the alpha secreted by "glucose-starved" cells was qualitatively and quantitatively similar to the effect of 0.56 mM glucose in the absence of butyrate. Likewise, 2 mM butyrate + 0.56 mM glucose was nearly equivalent to 5.6 mM glucose alone. These results demonstrate a novel effect of butyrate on glycoprotein biosynthesis; it is the only agent, reported thus far, which has the same effects as Glc or Man on protein glycosylation in "glucose-starved" cells.