ALTERATION OF PANCREATIC-ISLET IN DEVELOPING GK RATS PRIOR TO THE ONSET OF DIABETES

Adult Goto-Kakisaki rats (GK) present a Non-Insulin-Dependent Diabetes without obesity and were obtained by selective breeding. To determine whether modifications in islet pattern are involved in the subsequent appearance of diabetes, stereologic al and immunohistochemical analys es of pancreas were carried out in GK neonates. GK neonates displayed a lower body weight (BW) and pancreas weight than normal Wistar rats ( C). The islet mass (mg/g BW) was also low (68% of C) and small islets were abundant. The B-cell mass was low (56% of C); some B cells displa yed a highly abnormal subcellular morphology. The A-cell mass was high (295% of C) and A cells were unevenly located in some islets. The Pol ymorphous Endocrine Pancreatic cell Subpopulation (PEPS cells), a tran sitional cellular subtype between undifferentiated cells and terminall y differentiated B- or A cells, was quite absent. The endocrine cells were C > GK for B cells, GK much greater than C for A cells and C much greater than GK for PEPS cells. The lack of B-cell mass support the s ubsequent development of diabetes. The high abundance of A cells toget her with the insignificant number of PEPS cells indicate a genetically determined disruption in the pathways leading to a normal balance of endocrine cells in the islets.