(Journal Article): Pancreatic duodenal homeobox-1 and islet neogenesis associated protein: a possible combined marker of activateable pancreatic cell precursors.
 
Gagliardino JJ, Del Zotto H, Massa L, Flores LE, Borelli MI (CENEXA - Centre of Experimental and Applied Endocrinology (UNLP-CONICET, PAHO/WHO Collaborating Centre), National University of La Plata School of Medicine, La Plata, Argentina.)
 
IN: J Endocrinol 2003; 177(2):249-259
Impact Factor(s) of J Endocrinol: 3.319 (2004), 3.023 (2003), 2.834 (2001)

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ABSTRACT: The aim of this work was to study the possible relationship between pancreatic duodenal homeobox-1 (Pdx-1) and islet neogenesis-associated protein (INGAP) during induced islet neogenesis. Pregnant hamsters were fed with (S) and without (C) sucrose, and glycemia, insulin secretion in vitro, and pancreas immunomorphometric parameters were measured in their 7-day-old offspring. S offspring had significantly lower glycemic levels than C animals. Insulin release in response to increasing glucose concentrations in the incubation medium (2-16 mM glucose) did not increase in pancreata from either C or S offspring. However, pancreata from S offspring released more insulin than those from C animals. In S offspring, beta-cell mass, beta-cell replication rate and islet neogenesis increased significantly, with a simultaneous decrease in beta-cell apoptotic rate. INGAP- and Pdx-1-positive cell mass also increased in the islets and among acinar and duct cells. We found two subpopulations of Pdx-1 cells: INGAP-positive and INGAP-negative. Pdx-1/INGAP-positive cells did not stain with insulin, glucagon, somatostatin, pancreatic polypeptide, or neurogenin 3 antibodies. The increment of Pdx-1/INGAP-positive cells represented the major contribution to the Pdx-1 cell mass increase. Such increments varied among pancreas subsectors: ductal>insular>extrainsular. Our results suggested that INGAP participates in the regulation of islet neogenesis, and Pdx-1/INGAP-positive cells represent a new stem cell subpopulation at an early stage of development, highly activateable in neogenesis.

TYPE OF PUBLICATION: Original article

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• Street CN, Lakey JR, Rajotte RV, Shapiro AM, Kieffer TJ, Lyon JG, Kin T, Korbutt GS. Enriched Human Pancreatic Ductal Cultures Obtained from Selective Death of Acinar Cells Express Pancreatic and Duodenal Homeobox Gene-1 Age-Dependently. Rev Diabetic Stud 2004. 1: 66-79.
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