Rectification of diabetic state in C57BL/KsJ-db/db mice by the implantation of pancreatic beta cell line MIN6.

C57BL/KsJ mice carrying homozygous db/db mutation (db/db mice) are characterized by extreme obesity and early onset of hyperglycemia. In an attempt to rectify diabetes of these mice, a pancreatic beta cell line MIN6, which retains glucose-inducible insulin secretion, was transplanted subcutaneously into the back of the mice. Glucose and insulin levels of individual mice were examined biweekly and their weight gain weekly. All mice were sacrificed at 100 days after the transplantation of MIN6 cells. In db/db mice that had received MIN6 cells, blood insulin levels were restored and blood glucose levels were reduced to those of non-diabetic mice, although they remained obese. Glucose tolerance test suggested that transplanted MIN6 cells responded to loaded glucose as beta cells of non-diabetic mice. Immunohistochemical study showed that transplanted MIN6 cells produced insulin. Fatty liver associated with diabetes mellitus observed in db/db mice was not found in the MIN6 cell-transplanted mice. Implication of the results is discussed with reference to potential therapies for severe diabetes.