Placensin is a glucogenic hormone secreted by human placenta

FBN1 encodes asprosin, a glucogenic hormone, following furin cleavage of the C‐terminus of profibrillin 1. Based on evolutionary conservation between FBN1 and FBN2, together with conserved furin cleavage sites, we identified a peptide hormone placensin encoded by FBN2 based on its high expression in trophoblasts of human placenta. In primary and immortalized murine hepatocytes, placensin stimulates cAMP production, protein kinase A (PKA) activity, and glucose secretion, accompanied by increased expression of gluconeogenesis enzymes. In situ perfusion of liver and in vivo injection with placensin also stimulate glucose secretion. Placensin is secreted by immortalized human trophoblastic HTR‐8/SVneo cells, whereas placensin treatment stimulates cAMP‐PKA signaling in these cells, accompanied by increases in MMP9 transcripts and activities, thereby promoting cell invasion. In pregnant women, levels of serum placensin increase in a stage‐dependent manner. During third trimester, serum placensin levels of patients with gestational diabetes mellitus are increased to a bigger extent compared to healthy pregnant women. Thus, placensin represents a placenta‐derived hormone, capable of stimulating glucose secretion and trophoblast invasion. Synopsis This study identifies placensin as a glucogenic hormone that stimulates hepatic cAMP and glucose production, as well as invasion of placental cells. Serum placensin levels increase during pregnancy and this increase is higher in patients with gestational diabetes mellitus. Human placenta secretes a glucogenic hormone called placensin. Placensin stimulates hepatic glucose and cAMP production. Placesin also promotes placental cell invasiveness. Serum placensin levels increase during pregnancy. Patients with gestational diabetes mellitus display a more prominent increase in serum placensin levels. Graphical Abstract This study identifies placensin as a glucogenic hormone that stimulates hepatic cAMP and glucose production, as well as invasion of placental cells. Serum placensin levels increase during pregnancy and this increase is higher in patients with gestational diabetes mellitus.