Intrinsic regulators of pancreatic beta-cell proliferation.
Once thought incapable of significant proliferation, the pancreatic beta-cell has recently been shown to harbor immense powers of self-renewal. Pancreatic beta-cells, the sole source of insulin in vertebrate animals, can grow facultatively to a degree unmatched by other organs in experimental animals. beta-cell growth matches changes in systemic insulin demand, which increase during common physiologic states such as aging, obesity, and pregnancy. Compensatory changes in beta-cell mass are controlled by beta-cell proliferation. Here we review recent advances in our understanding of the intrinsic factors and mechanisms that control beta-cell cycle progression. Dysregulation of beta-cell proliferation is emerging as a fundamental feature in the pathogenesis of human disease states such as cancer and diabetes mellitus. New experimental observations and studies of these diseases suggest that beta-cell fate and expansion are coordinately regulated. We speculate on how these advances may accelerate the discovery of new strategies for the treatment of diseases characterized by a deficiency or excess of beta-cells.
Heit
Jeremy J
JJ
Departments of Developmental Biology and Medicine (Oncology Division), Stanford University School of Medicine, Stanford, California 94305, USA. seungkim@cmgm.stanford.edu
Karnik
Satyajit K
SK
Kim
Seung K
SK
D000818:Animals; D002453:Cell Cycle; D049109:Cell Proliferation; D044127:Epigenesis, Genetic; D006801:Humans; D050417:Insulin-Secreting Cells / Q000166:cytology*; D015398:Signal Transduction