Hyperplastic islets observed in "reversed" NOD mice treated without hematopoietic cells.
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.
Okubo
Yoshiaki
Y
Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi Shinjuku-ku, Tokyo 160-8582, Japan.
Shimada
Akira
A
Kanazawa
Yasuhiko
Y
Shigihara
Toshikatsu
T
Oikawa
Yoichi
Y
Imai
Takatoshi
T
Miyazaki
Junichi
J
Itoh
Hiroshi
H
D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000473:pathology* / Q000601:surgery*; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006965:Hyperplasia; D007328:Insulin / Q000235:genetics; D007371:Interferon-gamma / Q000235:genetics; D007515:Islets of Langerhans / Q000033:anatomy & histology / Q000473:pathology*; D016381:Islets of Langerhans Transplantation; D051379:Mice; D008813:Mice, Inbred ICR; D016688:Mice, Inbred NOD; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014184:Transplantation, Homologous / Q000502:physiology*
D007328:Insulin; D007371:Interferon-gamma