Investigators at the University of Pittsburgh (PA, USA) worked both with beta cell cultures and with human beta cells transplanted into the diabetic NOD-SCID mouse model. Their intent was to explore the presence, subcellular localization, and function of five early G1/S phase molecules - cyclins D1 -3 and -cdk4 and -cdk6 - in the adult human beta cell.

They reported in the August 2010 issue of the journal Diabetes that human beta cells contained easily detectable cdks 4 and 6 and cyclin D3 but variable amounts of cyclin D1. Cyclin D2 was only marginally detectable. All five molecules were principally cytoplasmic, not nuclear. Overexpression of the five, alone or in combination, led to variable increases in human beta-cell replication, with the cdk6/cyclin D3 combination being the most robust (15% versus 0.3% in control beta cells). A single molecule, cdk6, proved to be capable of driving human beta-cell replication in vitro and enhancing human islet engraftment/proliferation in vivo, superior to normal islets and as effectively as the combination of cdk6 plus a D-cyclin.

"Our team was the first to show that adult human beta cells can be induced to proliferate or grow at substantial rates, which no one thought possible before,” said senior author Dr. Andrew F. Stewart, professor of medicine at the University of Pittsburgh. "Now our effort has been to unravel these regulatory pathways to find the most effective strategy that will allow us to treat – and perhaps cure – diabetes by making new insulin-producing cells.”

The investigators warned that mice do not appear to make cdk6 naturally, but rather express cdk4 and cyclins D1 and D2. Thus, standard rodent studies of beta replication might have led researchers to incorrect conclusion in their quest to stimulate human beta cell replication.

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