Unraveling the pathophysiology of type 2 diabetes with a new selectively bred animal model, the Oikawa-Nagao mouse
(2025) In Diabetology International 16(1). p.13-22- Abstract
Type 2 diabetes (T2D) is a polygenic disease, and the development of animal models by selective breeding is crucial for understanding its etiology, pathophysiology, complications, and treatments. We recently developed a new T2D model, the Oikawa-Nagao (ON) mouse, by selectively breeding mice with inferior glucose tolerance [diabetes-prone (ON mouse DP®; ON-DP) strain] and superior glucose tolerance [diabetes-resistant (ON mouse DR®; ON-DR) strain] on a high-fat diet. ON-DP mice are predisposed to develop diabetes and obesity after being fed a high-fat diet, compared to ON-DR mice. These phenotypes provide valuable insights into the genetic and environmental interactions for the etiology of T2D. Our studies revealed that the emergence of... (More)
Type 2 diabetes (T2D) is a polygenic disease, and the development of animal models by selective breeding is crucial for understanding its etiology, pathophysiology, complications, and treatments. We recently developed a new T2D model, the Oikawa-Nagao (ON) mouse, by selectively breeding mice with inferior glucose tolerance [diabetes-prone (ON mouse DP®; ON-DP) strain] and superior glucose tolerance [diabetes-resistant (ON mouse DR®; ON-DR) strain] on a high-fat diet. ON-DP mice are predisposed to develop diabetes and obesity after being fed a high-fat diet, compared to ON-DR mice. These phenotypes provide valuable insights into the genetic and environmental interactions for the etiology of T2D. Our studies revealed that the emergence of these phenotypes is associated with novel pathophysiological mechanisms, such as low insulin secretion capacity associated with high CD36 expression in pancreatic β-cells and hypoleptinemia preceding obesity due to low leptin secretion capacity in adipocytes. In addition, ON-DP mice fed an atherogenic diet exhibit accelerated atherosclerosis, likely related to blood glucose fluctuations. These findings provide new perspectives on the pathogenesis of T2D and suggest potential prevention and treatment strategies. This review will present the development strategy of the ON mouse strain, representative metabolic phenotypes, and discuss the mechanisms driving these traits, and explore their relevance to human T2D and obesity.
(Less)
- author
- Nagao, Mototsugu LU
- publishing date
- 2025-01
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Diabetology International
- volume
- 16
- issue
- 1
- pages
- 13 - 22
- publisher
- Springer
- external identifiers
-
- pmid:39877441
- scopus:85213983502
- ISSN
- 2190-1678
- DOI
- 10.1007/s13340-024-00784-9
- language
- English
- LU publication?
- no
- additional info
- © The Japan Diabetes Society 2025. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
- id
- a00055a6-b404-4db1-ad6f-c18fb837c4ca
- date added to LUP
- 2025-02-01 21:56:43
- date last changed
- 2025-07-06 16:19:44
@article{a00055a6-b404-4db1-ad6f-c18fb837c4ca,
abstract = {{<p>Type 2 diabetes (T2D) is a polygenic disease, and the development of animal models by selective breeding is crucial for understanding its etiology, pathophysiology, complications, and treatments. We recently developed a new T2D model, the Oikawa-Nagao (ON) mouse, by selectively breeding mice with inferior glucose tolerance [diabetes-prone (ON mouse DP®; ON-DP) strain] and superior glucose tolerance [diabetes-resistant (ON mouse DR®; ON-DR) strain] on a high-fat diet. ON-DP mice are predisposed to develop diabetes and obesity after being fed a high-fat diet, compared to ON-DR mice. These phenotypes provide valuable insights into the genetic and environmental interactions for the etiology of T2D. Our studies revealed that the emergence of these phenotypes is associated with novel pathophysiological mechanisms, such as low insulin secretion capacity associated with high CD36 expression in pancreatic β-cells and hypoleptinemia preceding obesity due to low leptin secretion capacity in adipocytes. In addition, ON-DP mice fed an atherogenic diet exhibit accelerated atherosclerosis, likely related to blood glucose fluctuations. These findings provide new perspectives on the pathogenesis of T2D and suggest potential prevention and treatment strategies. This review will present the development strategy of the ON mouse strain, representative metabolic phenotypes, and discuss the mechanisms driving these traits, and explore their relevance to human T2D and obesity.</p>}},
author = {{Nagao, Mototsugu}},
issn = {{2190-1678}},
language = {{eng}},
number = {{1}},
pages = {{13--22}},
publisher = {{Springer}},
series = {{Diabetology International}},
title = {{Unraveling the pathophysiology of type 2 diabetes with a new selectively bred animal model, the Oikawa-Nagao mouse}},
url = {{http://dx.doi.org/10.1007/s13340-024-00784-9}},
doi = {{10.1007/s13340-024-00784-9}},
volume = {{16}},
year = {{2025}},
}