Expansion of pancreatic beta cells is a key goal of diabetes research, yet induction of adult human beta cell replication has proven frustratingly difficult. In part, this reflects a lack of understanding of cell cycle control in the human beta cell. Here, we provide a comprehensive immunocytochemical “atlas” of G1/S control molecules in the human beta cell. This “atlas” reveals that the majority these molecules, previously known to be present in islets, are actually present in the beta cell. More importantly, and in contrast to anticipated results, the “human beta cell G1/S atlas” reveals that almost all of the critical G1/S cell cycle control molecules are located in the cytoplasm of the quiescent human beta cell. Indeed, the only nuclear G1/S molecules are the cell cycle inhibitors, pRb, p57, and variably, p21: none of the cyclins or cdks necessary to drive human beta cell proliferation are present in the nuclear compartment. This observation may provide an explanation for the refractoriness of human beta cells to proliferation. Thus, in addition to known obstacles to human beta cell proliferation, restriction of G1/S molecules to the cytoplasm of the human beta cell represents an unanticipated obstacle to therapeutic human beta cell expansion.
- Received June 9, 2012.
- Accepted March 8, 2013.
- © 2013 by the American Diabetes Association.
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