Critical Mass of Purified Islets That Induce Normoglycemia After Implantation Into Dogs

Abstract

Twenty grafts of highly purified islets of Langerhans (mean ± SE vol 0.98 ± 0.3 ml, islet diam 122 ± 5 μm) were autoimplanted into the spleen or liver of totally pancreatectomized dogs. Portal venous pressure did not change significantly. Incremental doses of islets of 1000–3000 (n = 3), 3000–4000 (n = 6), 4000–5000 (n = 5), 5000–6000 (n = 3), and 6000–8000 (n = 3) per kilogram body weight resulted in corresponding fasting plasma glucose (PG) of 258 ± 18, 163 ± 13, 158 ± 17, 138 ± 15, and 108 ± 6 mg/dl. In 3 apancreatic control dogs, PG was 338 ± 9 mg/dl. One (normoglycemic) dog died of wound complications, and follow-up PG at 1 mo was 89 ± 5 mg/dl in 6 of 10 dogs that received 3000–5000 islets/kg and 91 ± 6 mg/dl in all 6 that received > 5000 islets/kg. K values 1 mo after surgery during glucose tolerance tests were 1.8 ± 0.3 for 6 spleen dogs and 1.6 ± 0.3 for 6 liver dogs. Six months after splenic implantation, PG was 75 ± 4 mg/dl and rose to > 350 mg/dl after splenectomy. These data define the critical number of purified dog islets of known size that is necessary to induce prolonged normoglycemia. Sufficient pure islets can be collected from 1 dog pancreas to correct diabetes after autoimplantation into the liver or spleen.