Abstract

Spontaneously Diabetic Torii (SDT) rat is a model of severe type 2 diabetes and its complications. These characteristics of SDT rat are very useful to research diseases; however, the slow onset of diabetes may limit the usefulness of this animal model. To solve this problem, we performed bilateral midbrain transection on SDT rats and evaluated whether hyperphagia accelerates the onset of diabetes. By severing ascending fibers from the nucleus tractus solitarius to limbic regions through ventral and dorsal tegmental regions, food consumption was significantly increased in SDT rats and the onset of diabetes was accelerated. Cumulative incidence of diabetes in midbrain transected SDT rats was 88.9% at 7 weeks after surgery (14 weeks of age), while sham operated rats was 20.0%. Increased food consumption was correlated to body weight, plasma glucose level, plasma triglyceride level, and plasma insulin level. In conclusion, the overeating caused by blocking anorexigenic signal in brain significantly accelerates the onset of diabetes in SDT rats. The early development of type 2 diabetes may accelerate microvascular complications and is considered useful in the study of the disease in SDT rats.

Highlights

  • Diabetes is one of the most common metabolic diseases

  • Severe diabetes and its microvascular complications spontaneously develop in this animal model, the diabetes takes too long to develop, making this animal model cumbersome to use as a research tool

  • We fed Spontaneously Diabetic Torii (SDT) rats highfat diet (HFD) because we hypothesized that such a diet would accelerate the onset of diabetes in this model; the HFD caused hypersecretion of insulin from pancreatic β-cells in SDT rats [19]

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Summary

INTRODUCTION

Diabetes is one of the most common metabolic diseases. According to the International Diabetes Federation (IDF), 463 million adults are living with this disease and the number of adult patients is expected to increase to 700 million by 2045 [1]. An animal models of non-obese type 2 diabetes have been developed following the need for testing of various drugs [3]. The Spontaneously Diabetic Torii (SDT) rat is a model of non-obese type 2 diabetes and is reported to develop significant hyperglycemia with severe diabetic complications in eyes, kidneys, and peripheral nerves [4,5]. These SDT rat features are very useful for investigation purposes; their slow development Because excess intake of a high-calorie diet or overeating is known to accelerate the onset of diabetes in animal models, such as Otsuka-Long-Evans-Tokushima Fatty (OLETF) rats [7], we performed bilateral midbrain transection on SDT rats before diabetes developed and evaluated whether overeating accelerates the onset of diabetes in this animal model

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