Blocking a Cell Cycle Inhibitor Stimulates Replication of Insulin-Producing Beta Cells

It is a negative regulator of cell proliferation and may play a role in the maintenance of the nonproliferative state throughout life. It is expressed in the heart, brain, lung, skeletal muscle, kidney, pancreas, and testis.

Investigators at the University of Pennsylvania (Philadelphia, USA) and their colleagues at the Hebrew University of Jerusalem (Israel) used short hairpin RNA (shRNA) to suppress the CDKN1C gene in human beta cells obtained from deceased adult donors.

They reported in the January 16, 2014, online edition of the Journal of Clinical Investigation that when human pancreatic tissue with inhibited p57Kip2 activity was transplanted into hyperglycemic, immunodeficient mice, beta cell replication increased more than three-fold. The newly replicated cells retained properties of mature beta cells, including the expression of beta cell markers such as insulin, PDX1, and NKX6.1. Furthermore, these newly replicated cells demonstrated normal glucose-induced calcium influx, further indicating beta cell functionality.

These results showed that beta cells from older humans, in which baseline replication is negligible, could be coaxed to reenter and complete the cell cycle while maintaining mature beta cell properties. Controlled manipulation of this pathway holds promise for the expansion of beta cells in patients with type II diabetes.

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University of Pennsylvania
Hebrew University of Jerusalem