Secondary diabetes following pancreatectomy in the dog was prevented by autotransplantation of pancreatic fragments in the spleen. The function and composition of the endocrine elements were analyzed by functional studies and by light and electron microscopy at 4, 8, and 24 weeks. During these different periods, splenectomy proved that all the animals were dependent on the transplanted tissue for normoglycemia. The morphologic study of the spleen showed the survival of the intrinsic pancreatic ganglia as well as the presence of an amyelinic, terminal nervous network, with adrenergic varicosities, exclusively related to the endocrine dements.Nerve endings were identified in close contact with beta, alpha-2, and alpha-1 cells, either isolated in the splenic pulp or forming insular structures with a variable size and composition. No cholinergic varicosities could be identified nor was there any innervation in the ductal and acinar tissue.From 4 weeks on, Schwann cells could be seen coating large surfaces of the endocrine cells at the same time as they sheathed nervous elements, thus creating true "neuroinsular complexes" with beta and alpha-2 cells. The few ganglia that could only be identified under light microscopy, as well as the ultrastructural characteristics of the innervation, suggest that the sympathetic fibers of the perivascular, trabecular and capsular plexus of the spleen had grown and invaded the inoculated endocrine tissue in the splenic pulp.

As far as we know, after adult enzyme-digested pancreatic fragment autotransplantation, the fate of the inoculated pancreatic tissue has never been reported and the hypothetic engrafted islet mass growth by mitotic division or by a true islet neogenesis from ductular precursor cells has never been demonstrated. In dogs with total or near-total (90%) pancreatectomy that preserves the duodenum and the common bile duct, morphologic study of the pancreatic tissue inoculated into the spleen has demonstrated an exuberant ductular-acinar-islet regenerative process, with progressive cystic degeneration of the newly formed ductular-acinar structures occurring simultaneously with the selective survival and growing predominance of extraductal tissue scattered as distinct islets, clusters of islet cells, or single islet cells. In addition to the B, A2, and D cell types of the normal adult dog islet, we have also seen a peculiar ultrastructural pleomorphism of the insular B cells, frequently combined with their ductular or glandular arrangement in maturing islets. Rare or never before reported islet cell types in the adult dog's islets (G cells, mixed endocrine cells of the A2-D, D-B, and A2-B types, and mixed acinar-islet cells of the D-acinar type) were also putatively identified. Using light microscopy we have identified many mitotic figures on ductular and centroacinar cells in ductules and ductular-acinar structures.(ABSTRACT TRUNCATED AT 250 WORDS)

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After autotransplantation of pancreatic fragments into the dog's spleen, the morphogenesis of the reinnervating process has evolved as an highly differentiated model, reproducing the most peculiar and systematic relationships between schwann cells, axons, and islet cells reported in the dog's islet, despite it's modulation by the restrictive conditions derived from the intrasplenic location of the dispersed pancreatic tissue. The reinnervating process is described, emphasizing the peculiar ultrastructural features and topography of the schwann cells and of the axonal network that impose the concept of a true anatomical reinnervation, which make previsible the possibility of a very selective and direct neurochemical and/or electrotonic control of the engrafted islet cells. The schwann-axon-islet complexes are a very peculiar and regular arrangement between islet cells and nervous elements and are reproduced after the autotransplant without the engrafted ganglia, whose potential but aleatory contribution could not be unequivocally characterized. Axonal profiles or schwann cells on the abundant regenerated ductal-acinar structures were not identified.