Biochemical and Biophysical Research Communications, Vol.524, No.1, 22-27, 2020
The role of bone-derived PDGF-AA in age-related pancreatic beta cell proliferation and function
The occurrence of type 2 diabetes(T2D) increases with age. The platelet-derived growth factor (PDGF) is one of the key factors regulating beta cell proliferation and function, but the contribution of PDGF signaling in beta cells aging and senescence remains unexplored. Here, we showed that the level of both serum and tissue PDGF-AA decreased with age, and the serum PDGF-AA level was positively correlated with beta cell proliferation and function in aging. The decline of PDGF-AA level in aging was partly due to decreased number as well as secretion of osteoblast lineage cells in bone tissue. Conditioned medium from osteoblast lineage cells induced insulinoma b cells proliferation and insulin secretion in vitro, while addition of PDGF-AA neutralizing antibody attenuated this effect. Transplantation of juvenile osteoblast lineage cells increased serum PDGF-AA level and promoted b cell proliferation and function in aging mice, which eventually resulted in better glucose tolerance. Taken together, these findings revealed the role of decreased bone-derived PDGF-AA in mediating the disrupted proliferation and function of beta cells in aging. (C) 2020 The Authors. Published by Elsevier Inc.