PARACRINE AUTOCRINE REGULATION OF PANCREATIC LET CELL-PROLIFERATION AND DIFFERENTIATION IN THE HAMSTER - STUDIES USING PARABIOSIS/

Partial obstruction of the pancreatic duct in hamsters leads to new is let formation and reversal of streptozotocin diabetes. The purpose of this study was to delineate the mechanism by which endocrine cell prol iferation and differentiation is mediated in this model. Six pairs of parabiotic hamsters were established and partial duct obstruction was inducted in 1 parabiont from each pair. At 6 weeks, the pancreatic wei ght (mg/100g bw); DNA (mu g/100g bw) and protein content (mg/100g bw) showed 28% (167 +/- 21 vs. 130 +/- 17), 32% (1,052 +/- 206 vs. 795 +/- 159), and 20% (25.4 +/- 6.6 vs. 21.2 +/- 1.9) increases (p < 0.05), r espectively, over the non-wrapped parabionts. Morphometric analysis de monstrated the presence of new islets in the wrapped pancreata with a 100% increase in the number of islets/mm(2) compared with non-wrapped controls (0.90 +/- 0.5 vs. 1.8 +/- 0.7, p < 0.01). A cytosol extract w as prepared from duct-obstructed pancreases, and 4 mu l/g bw injected i.p. twice daily for 2 d produced significant increases in pancreatic weight and DNA content of 12% and 40%, respectively. Cytosol extract f rom non-wrapped pancreata had no effects compared with saline. When wr apped cytosol extract was injected for 21 d, the labeling index of duc tular and islet cells (% cell nuclei labeled with H-3-TdR) was increas ed 10- and 6-fold respectively over controls (2.42 +/- 0.28 vs. 0.23 /- 0.01 and 1.17 +/- 0.01 vs. 0.25 +/- 0.04, respectively, p < 0.01). The trophic effects observed in this model of islet cell proliferation and differentiation did not appear to be mediated by a humoral mechan ism because the changes induced by partial obstruction were not observ ed in the non-operated parabiont. Control of pancreatic endocrine cell growth in this model appears to involve paracrine and/or autocrine re gulatory mechanisms.