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  • Title: Hyperplastic islets observed in "reversed" NOD mice treated without hematopoietic cells.
    Author: Okubo Y, Shimada A, Kanazawa Y, Shigihara T, Oikawa Y, Imai T, Miyazaki J, Itoh H.
    Journal: Diabetes Res Clin Pract; 2008 Jan; 79(1):18-23. PubMed ID: 17919765.
    Abstract:
    At the onset of type 1 diabetes, most of the insulin-producing pancreatic beta cells are destroyed by effector cells, and therefore, the following two factors, at a minimum, are necessary for "reversing" hyperglycemia in autoimmune diabetes; depletion of effector cells and enhancement of beta cell regeneration. In this study, we tried a novel approach for "reversing" autoimmune diabetes in a murine model. Here we show that remission could be achieved with a combination therapy of a single injection of complete Freund's adjuvant (CFA) and a single intraperitoneal injection of a pancreatic beta cell line, MIN6N-9a, in recent-onset diabetic NOD (non-obese diabetic) mice. Five out of seven mice (71%) receiving MIN6N-9a and CFA became normoglycemic within 120 days after treatment, whereas only two of nine (22%) receiving vehicle instead of MIN6N-9a achieved remission. Histological examination of pancreatic specimens from "reversed" mice showed decreased islet number, but each islet was markedly hyperplastic; being about six times larger than those from controls. Although it has been reported that hematopoietic cells such as splenocytes differentiate into insulin-producing cells and play a key role, our data indicate that they are not an absolute requirement for the "reversal" of autoimmune diabetes.
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