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Endocrinology Vol. 138, No. 4 1750-1762
Copyright © 1997 by The Endocrine Society

ARTICLES

Differentiation of New Insulin-Producing Cells Is Induced by Injury in Adult Pancreatic Islets1

A. Fernandes, L. C. King, Y. Guz, R. Stein, C. V. E. Wright and G. Teitelman

Department of Anatomy and Cell Biology (A.F., L.C.K., Y.G., G.T.), SUNY Health Science Center at Brooklyn, Brooklyn, New York 11203; Department of Cell Biology (C.V.E.W.), Vanderbilt University Medical Center, Nashville, Tennessee 37232; and the Department of Molecular Physiology and Biophysics (R.S.), Vanderbilt University Medical Center, Nashville, Tennessee 37232

Address all correspondence and requests for reprints to: Dr. Gladys Teitelman, Department of Anatomy and Cell Biology, SUNY Health Science Center at Brooklyn, Brooklyn, New York 11203.

The ability of the adult pancreas to generate new insulin (ß) cells has been controversial because of difficulties in unequivocally identifying the precursor population. We recently determined that ß cells were generated during development from precursors that expressed the homeodomain-containing transcription factor pancreas duodenum homeobox gene-1 (PDX-1). To investigate whether PDX-1+ stem cells are present in adult pancreas, we examined two animal models of diabetes. One model was produced by injecting adult mice with streptozotocin (SZ), a toxin that produces hyperglycemia due to rapid and massive ß cell death. After SZ-mediated elimination of existing IN+/PDX-1+ cells, a population of somatostatin (SOM)+/PDX-1+ cells, a cell type thought to represent an embryonic islet precursor cell, appeared in islets. The appearance of SOM+/PDX-1+ cells was followed in time by the differentiation to SOM+/IN+/PDX-1+cells. SOM+/PDX-1+ cells also appeared in islets of nonobese diabetic mice, a strain of mice in which ß cell destruction is immune-mediated. Our findings establish the existence of PDX-1+ ß cell precursors in the adult pancreas and indicate that their differentiation is induced by islet injury .




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