ISLET-CELL REGENERATION IN THE DIABETIC HAMSTER PANCREAS WITH RESTORATION OF NORMOGLYCEMIA CAN BE INDUCED BY A LOCAL GROWTH FACTOR(S)

Partial pancreatic duct obstruction in the hamster leads to the induct ion of endocrine-cell differentiation and new islet formation. We prep ared cytosolic extracts fi-om the partially obstructed pancreas and id entified one, which when administered i.p., produced significant incre ases in the incorporation of tritiated thymidine by ductular and islet cells, as well as a corresponding increase in islet mass. In this stu dy, we evaluate the ability of this extract to reverse streptozotocin diabetes mellitus. Hamsters were treated i.p. twice daily for 7 weeks with either 0.9% NaCl (saline) (n = 10) or a cytosol extract (n = 10) prepared previously from partially obstructed hamster pancreata. All a nimals in the cytosol group survived vs only 60% of the saline group ( p = 0.02). Random blood glucose levels were greater than 22.2 mmol/l i n 90% of the saline group vs 40% in the cytosol group (p < 0.05). Panc reatic tissue from the surviving saline animals and from persistently hyperglycaemic cytosol-treated animals, showed intra-cytoplasmic vacuo lation of islet cells, a characteristic lesion of sustained hyperglyca emic states. Vacuolation was not observed in normoglycaemic extract tr eated animals. Islets in hyperglycaemic animals demonstrated a profoun d decrease or absence of immunoreactive insulin, compared to an abunda nce of immunoreactive beta cells in cytosol-treated animals that rever ted to normoglycaemia. In this group, single cells or nests of cells s tained for insulin or glucagon cells were identified in ductal epithel ium in association with cells budding from the duct. Morphometric anal ysis of pancreata in reverted cytosol-treated animals showed a new pop ulation of small islets compared with saline controls and an increased islet mass. In summary, streptozotocin diabetes can be reversed by ne w islet formation induced by local pancreatic growth factors, the exac t nature of which remains to be determined.