title: Measurement of pancreatic islet cell proliferation by heavy water labeling.
abstract: 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 ((2)H) from heavy water ((2)H(2)O) 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, approximately 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.
authors.affiliation: KineMed Inc, Emeryville, CA 94608, USA. schen@kinemed.com
authors.forename: Songyuan
authors.initials: S
authors.lastname: Chen
authors.forename: Scott
authors.initials: S
authors.lastname: Turner
authors.forename: Ellen
authors.initials: E
authors.lastname: Tsang
authors.forename: Julie
authors.initials: J
authors.lastname: Stark
authors.forename: Holly
authors.initials: H
authors.lastname: Turner
authors.forename: Ablatt
authors.initials: A
authors.lastname: Mahsut
authors.forename: Keri
authors.initials: K
authors.lastname: Keifer
authors.forename: Michelle
authors.initials: M
authors.lastname: Goldfinger
authors.forename: Marc K
authors.initials: MK
authors.lastname: Hellerstein
mesh_terms: D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D048708:Cell Growth Processes / Q000502:physiology; D017666:Deuterium Oxide / Q000378:metabolism*; D008401:Gas Chromatography-Mass Spectrometry; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar
chemical_list: D001973:Bromodeoxyuridine; D017666:Deuterium Oxide