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Summary: Cholecystokinin Is Up-Regulated in Obese Mouse
Islets and Expands -Cell Mass by Increasing -Cell
Survival
Jeremy A. Lavine,* Philipp W. Raess,* Donald S. Stapleton, Mary E. Rabaglia,
Joshua I. Suhonen, Kathryn L. Schueler, James E. Koltes, John A. Dawson,
Brian S. Yandell, Linda C. Samuelson, Margery C. Beinfeld, Dawn Belt Davis,
Marc K. Hellerstein, Mark P. Keller, and Alan D. Attie
Departments of Biochemistry (J.A.L., P.W.R., D.S.S., M.E.R., J.I.S., K.L.S., J.E.K., D.B.D., M.P.K., A.D.A.),
Statistics (J.A.D., B.S.Y.), and Medicine, Section of Endocrinology (D.B.D.), University of Wisconsin,
Madison, Wisconsin 53706; Department of Molecular and Integrative Physiology (L.C.S.), University of
Michigan, Ann Arbor, Michigan 48109; Department of Pharmacology and Experimental Therapeutics
(M.C.B.), Tufts University, Boston, Massachusetts 02111; and Department of Nutritional Sciences and
Toxicology (M.K.H.), University of California, Berkeley, Berkeley, California 94720
An absolute or functional deficit in -cell mass is a key factor in the pathogenesis of diabetes. We
model obesity-driven -cell mass expansion by studying the diabetes-resistant C57BL/6-Leptinob/ob
mouse.Wepreviouslyreportedthatcholecystokinin(Cck)wasthemostup-regulatedgeneinobese
pancreatic islets. We now show that islet cholecystokinin (CCK) is up-regulated 500-fold by obesity
and expressed in both - and -cells. We bred a null Cck allele into the C57BL/6-Leptinob/ob
back-
ground and investigated -cell mass and metabolic parameters of Cck-deficient obese mice. Loss
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