Hyperplastic islets observed in "reversed" NOD mice treated without hematopoietic cells

Yoshiaki Okubo, Akira Shimada, Yasuhiko Kanazawa, Toshikatsu Shigihara, Yoichi Oikawa, Takatoshi Imai, Junichi Miyazaki, Hiroshi Itoh

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)18-23
Number of pages6
JournalDiabetes Research and Clinical Practice
Volume79
Issue number1
DOIs
Publication statusPublished - 2008 Jan 1

Keywords

  • Adjuvant
  • MIN6
  • NOD mouse
  • Regeneration
  • Type 1 diabetes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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