New analytical method for pancreas and liver regeneration: normalization of streptozotocin-induced hyperglycemia by retrograde injection of insulin producing cells.

We established a new analytical system in which functioning cells were transplanted directly into the pancreas and liver. The retrograde transplantation of beta cell line, Min6 cells, into the streptozotocin-diabetic mice normalized plasma glucose and insulin levels. The injected cells were protected from pancreatic enzymes with enzyme inhibitor. Blood glucose decreased gradually over 10 days and the diabetic mice recovered weight at the same time. Intraperitoneal glucose tolerance test showed that the peak of plasma glucose of the transplanted mice was less than half that of the control. The insulin secretion of the transplanted mice was recovered and stimulated 4.6 times from the basal secretion. Histological analyses showed that the pancreas and liver were characterized by Min6 cell clusters dispersed throughout the organs. Min6 cells were detected near the pancreatic or bile ducts. It is suggested that the injected cells obstructed the peripheral ducts where they settled. The weight of pancreas and liver did not differ significantly in either Min6 transplanted or the control mice. The metabolic effects on the weights of these organs appeared the same in both groups. This is the first report that cells transplanted via ducts into the pancreas and liver performed their biological function. Our transplantation model makes possible the in vivo analysis of the regeneration machinery of the pancreas and liver.