Abstract
A better understanding of pathogenic mechanisms is required in order to treat diseases. However, the mechanisms of diabetes mellitus and diabetic complications are extremely complex. Immune reactions are involved in the pathogenesis of diabetes and its complications, while diabetes influences immune reactions. Furthermore, both diabetes and immune reactions are influenced by genetic and environmental factors. To address these issues, animal models are useful tools. So far, various animal models of diabetes have been developed in rats, which have advantages over mice models in terms of the larger volume of tissue samples and the variety of type 2 diabetes models. In this review, we introduce rat models of diabetes and summarize the immune reactions in diabetic rat models. Finally, we speculate on the relationship between immune reactions and diabetic episodes. For example, diabetes-prone Biobreeding rats, type 1 diabetes model rats, exhibit increased autoreactive cellular and inflammatory immune reactions, while Goto-Kakizaki rats, type 2 diabetes model rats, exhibit increased Th2 reactions and attenuation of phagocytic activity. Investigation of immunological abnormalities in various diabetic rat models is useful for elucidating complicated mechanisms in the pathophysiology of diabetes. Studying immunological alterations, such as predominance of Th1/17 or Th2 cells, humoral immunity, and innate immune reactions, may improve understanding the structure of amplification circuits for diabetes in future studies.
Highlights
The prevalence of diabetes mellitus (DM) is increasing in developed countries, including Japan
Fulminant type 1 DM, which represents 20% of acute-onset type 1 DM, is not related to autoreactive immune responses [13]. Other pathological processes, such as slowly progressive insulin-dependent diabetes mellitus (SPIDDM), or latent autoimmune diabetes in adults (LADA), which result from gradual distraction of islets of Langerhans in pancreas through an autoimmune response, are difficult to distinguish from type 2 DM [14, 15]
Free fatty acid-bound fetuinA has been shown to be an endogenous ligand for toll-like receptor 4 (TLR4) [76], and hyperglycemia has been shown to enhance IL-1β secretion [77]
Summary
The prevalence of diabetes mellitus (DM) is increasing in developed countries, including Japan. A determinant in the pathogenesis of diabetes and diabetic complications, is associated with various immune reactions in patients with diabetes. An accumulation of information on immune reactions associated with diabetic episodes is required in order to achieve a better understanding of its pathogenic mechanisms. Animal models of DM are useful for investigating the relationship between immune reactions and diabetic episodes. Various type 2 DM models have been developed in rats. Peripheral blood from rats can be collected in more than 10-fold volume as compared to blood from mice. Blood specimens from humans usually consist of peripheral blood, and the diabetic rat is a valuable experimental model for application to laboratory test. We summarize the diverse diabetic rat models and discuss the relationship between diabetic episodes and immune reactions
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