Serum from pregnant donors induces human beta cell proliferation and insulin secretion

Pancreatic beta cells are among the slowest replicating cells in the human body. Human beta cells usually do not increase in number with exceptions being during the neonatal period, in cases of obesity, and during pregnancy. This project explored maternal serum for stimulatory potential on human beta cell proliferation and insulin output. Gravid, full-term women who were scheduled to undergo cesarean delivery were recruited for this study. A human beta cell line was cultured in media supplemented with serum from pregnant and non-pregnant donors and assessed for differences in proliferation and insulin secretion. A subset of pregnant donor sera induced significant increases in beta cell proliferation and insulin secretion. Pooled serum from pregnant donors also increased proliferation in primary human beta cells but not primary human hepatocytes indicating a cell-type specific effect. This study suggests stimulatory factors in human serum during pregnancy could provide a novel approach for human beta cell expansion.

[1]  Seung K. Kim,et al.  Lactation improves pancreatic β cell mass and function through serotonin production , 2020, Science Translational Medicine.

[2]  Diane C. Saunders,et al.  Serotonin Regulates Adult β-Cell Mass by Stimulating Perinatal β-Cell Proliferation , 2019, Diabetes.

[3]  M. German,et al.  (Re)generating Human Beta Cells: Status, Pitfalls, and Perspectives. , 2018, Physiological reviews.

[4]  J. Ahnfelt-Rønne,et al.  The EndoC-βH1 cell line is a valid model of human beta cells and applicable for screenings to identify novel drug target candidates , 2017, Molecular metabolism.

[5]  R. Retnakaran Adiponectin and β-Cell Adaptation in Pregnancy , 2017, Diabetes.

[6]  S. Baekkeskov,et al.  Advances in pancreatic islet monolayer culture on glass surfaces enable super-resolution microscopy and insights into beta cell ciliogenesis and proliferation , 2017, Scientific Reports.

[7]  J. Schaack,et al.  Adiponectin Deficiency Impairs Maternal Metabolic Adaptation to Pregnancy in Mice , 2017, Diabetes.

[8]  P. Wang,et al.  Development of a reliable automated screening system to identify small molecules and biologics that promote human β-cell regeneration. , 2016, American journal of physiology. Endocrinology and metabolism.

[9]  M. German,et al.  β‐Cell adaptation in pregnancy , 2016, Diabetes, obesity & metabolism.

[10]  Peng Wang,et al.  Induction of human pancreatic beta cell replication by inhibitors of dual specificity tyrosine regulated kinase , 2015, Nature Medicine.

[11]  A. F. Stewart,et al.  Human β-Cell Proliferation and Intracellular Signaling Part 2: Still Driving in the Dark Without a Road Map , 2014, Diabetes.

[12]  G. Morahan,et al.  Faculty Opinions recommendation of Serotonin regulates pancreatic beta cell mass during pregnancy. , 2010 .

[13]  C. Cobelli,et al.  Adaptive changes in pancreatic beta cell fractional area and beta cell turnover in human pregnancy , 2010, Diabetologia.

[14]  I. Rooman,et al.  Regulation of pancreatic beta-cell mass. , 2005, Physiological reviews.