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Am J Physiol Endocrinol Metab 293: E1459-E1464, 2007. First published August 28, 2007; doi:10.1152/ajpendo.00375.2007 Free Article
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INNOVATIVE METHODOLOGY

Measurement of pancreatic islet cell proliferation by heavy water labeling

Songyuan Chen,1 Scott Turner,1 Ellen Tsang,1 Julie Stark,1 Holly Turner,1 Ablatt Mahsut,1 Keri Keifer,1 Michelle Goldfinger,1 and Marc K. Hellerstein2,3

1KineMed, Inc., Emeryville; 2Department of Nutritional Sciences and Toxicology, University of California at Berkeley, Berkeley; and 3Division of Endocrinology and Metabolism, Department of Medicine, San Francisco General Hospital, University of California at San Francisco, San Francisco, California

Submitted 16 June 2007 ; accepted in final form 16 August 2007

We describe a sensitive technique for measuring long-term islet cell proliferation rates in vivo in rats. Pancreatic islets were isolated and the incorporation of deuterium (2H) from heavy water (2H2O) into the deoxyribose moiety of DNA was measured by GC-MS. The results of heavy water labeling and BrdU staining were compared. The two methods were highly correlated (r = 0.9581, P < 0.001). Based on long-term heavy water labeling, ~50% of islet cells divided in rats between 8 and 15 wk of age. Of interest, long-term BrdU administration suppressed proliferation of islet cells significantly, but not of bone marrow cells. Physiological evidence further supported the validity of the method: older animals (24 wk old) had 60% lower islet cell proliferation rates than younger rats (5 wk old), and partial (50%) pancreatectomy increased proliferation by 20%. In addition, cholecystokinin-8 treatment significantly stimulated proliferation in pancreatectomized rats only. In summary, heavy water labeling is a quantitative approach for measuring islet cell proliferation and testing therapeutic agents.

diabetes; beta-cell; 5-bromodeoxyuridine; sulfated cholecystokinin-8


Address for reprint requests and other correspondence: S. Chen, KineMed, Inc., 5980 Horton St., Ste 400, Emeryville, CA 94608 (e-mail: schen{at}kinemed.com) or M. K. Hellerstein (e-mail: march{at}nature.berkeley.edu)




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[Abstract] [Full Text] [PDF]


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