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

Fingerprint

Inbred NOD Mouse
Type 1 Diabetes Mellitus
Freund's Adjuvant
Insulin-Secreting Cells
Insulin
Intraperitoneal Injections
Hyperglycemia
Regeneration
Cell Line
Injections
Therapeutics

Keywords

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

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Hyperplastic islets observed in "reversed" NOD mice treated without hematopoietic cells. / Okubo, Yoshiaki; Shimada, Akira; Kanazawa, Yasuhiko; Shigihara, Toshikatsu; Oikawa, Yoichi; Imai, Takatoshi; Miyazaki, Junichi; Itoh, Hiroshi.

In: Diabetes Research and Clinical Practice, Vol. 79, No. 1, 01.2008, p. 18-23.

Research output: Contribution to journalArticle

Okubo, Yoshiaki ; Shimada, Akira ; Kanazawa, Yasuhiko ; Shigihara, Toshikatsu ; Oikawa, Yoichi ; Imai, Takatoshi ; Miyazaki, Junichi ; Itoh, Hiroshi. / Hyperplastic islets observed in "reversed" NOD mice treated without hematopoietic cells. In: Diabetes Research and Clinical Practice. 2008 ; Vol. 79, No. 1. pp. 18-23.
@article{24124bc9a1af4de0be939b4cb9f4d284,
title = "Hyperplastic islets observed in {"}reversed{"} NOD mice treated without hematopoietic cells",
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.",
keywords = "Adjuvant, MIN6, NOD mouse, Regeneration, Type 1 diabetes",
author = "Yoshiaki Okubo and Akira Shimada and Yasuhiko Kanazawa and Toshikatsu Shigihara and Yoichi Oikawa and Takatoshi Imai and Junichi Miyazaki and Hiroshi Itoh",
year = "2008",
month = "1",
doi = "10.1016/j.diabres.2007.08.020",
language = "English",
volume = "79",
pages = "18--23",
journal = "Diabetes Research and Clinical Practice",
issn = "0168-8227",
publisher = "Elsevier Ireland Ltd",
number = "1",

}

TY - JOUR

T1 - Hyperplastic islets observed in "reversed" NOD mice treated without hematopoietic cells

AU - Okubo, Yoshiaki

AU - Shimada, Akira

AU - Kanazawa, Yasuhiko

AU - Shigihara, Toshikatsu

AU - Oikawa, Yoichi

AU - Imai, Takatoshi

AU - Miyazaki, Junichi

AU - Itoh, Hiroshi

PY - 2008/1

Y1 - 2008/1

N2 - 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.

AB - 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.

KW - Adjuvant

KW - MIN6

KW - NOD mouse

KW - Regeneration

KW - Type 1 diabetes

UR - http://www.scopus.com/inward/record.url?scp=37549022620&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=37549022620&partnerID=8YFLogxK

U2 - 10.1016/j.diabres.2007.08.020

DO - 10.1016/j.diabres.2007.08.020

M3 - Article

VL - 79

SP - 18

EP - 23

JO - Diabetes Research and Clinical Practice

JF - Diabetes Research and Clinical Practice

SN - 0168-8227

IS - 1

ER -