Autotransplantation of pancreatic islets without separation of exocrine and endocrine tissue in totally pancreatectomized dogs

An attempt was made to determine whether diabetes could be ameliorated in dogs by autotransplantation of pancreatic fragments to the spleen and to determine the optimal time of collagenase digestion for pancreatic tissue dispersal. In all, 48 dogs were made diabetic by total pancreatectomy; 15 dogs not further treated survived 7.0 ± 1.1 (SE) days with a mean plasma glucose of 401 ± 5 (SE) mg/100 ml 2 days after pancreatectomy. The pancreases of 33 dogs were distended with Hanks' solution, minced, digested with collagenase (600 microns/ml of tissue), for 0 to 25 min, and autotransplanted to the splenic pulp. The incidence of permanent normoglycemia (fasting plasma glucose & 150 mg/100 ml) and the K value of glucose tolerance tests (GTT) performed 2 and 10 wk after transplant were determined in groups divided according to the length of collagenase digestion. All 5 dogs receiving undigested tissue remained hyperglycemic. One of 7 dogs receiving tissue digested for 10 min became normoglycemic. In contrast, 7 of 8, 7 of 7, and 6 of 6 dogs receiving tissue digested for 15, 20, and 25 min, respectively, became normoglycemic (followed for 6 mth). K values at 2 wk were 1.20 ± 1.19 (SE)%, 1.60 ± 0.25 (SE)%, and 0.78 ± 0.08 (SE)% in the normoglycemic dogs of the 15, 20, and 25 min digestion groups, respectively. The K value of normal dogs was 3.30 ± 0.27 (SE)%. The glucose tolerance curves of the 20 min group at 2 and 10 wk most nearly approximated the curves of normal dogs. K values improved in all recipient dogs. Diabetes recurred immediately and death occurred at a mean of 4.8 ± 1.5 days in 12 recipient dogs following splenectomy. It is concluded that pancreatic fragments can be successfully autotransplanted to the spleen without separation of endocrine and exocrine tissue and that 20 min is the optimal period of collagenase digestion for tissue preparation.