Pancreatic duodenal homeobox-1 and islet neogenesis-associated protein: a possible combined marker of activateable pancreatic cell precursors

GAGLIARDINO JJ; DEL ZOTTO H; MASSA ML; FLORES LE; BORELLI MI

JOURNAL OF ENDOCRINOLOGY

Society for Endocrinology and BioScientifica Ltd

Lugar: Bristol; Año: 2003 vol. 177 p. 249 - 259

0022-0795

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 o.spring. S o.spring 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 o.spring. However, pancreata from S o.spring released more insulin than those from C animals. In S o.spring, _-cell mass, _-cell replication rate and islet neogenesis increased significantly, with a simultaneous decrease in B-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/INGAPpositive 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.