Functional role of natural killer T cells in non-obese pre-diabetes model mice
Pre-diabetic patients have a high risk of developing diabetes as well as other associated diseases. From the viewpoint of risk assessment and to assist the development of protective therapies, we focused on the functional role of natural killer T (NKT) cells in pre-diabetes. We found that the expression of an NKT cell marker gene, Va14-Ja18, was significantly lower in specific tissues/organs such as adipose tissue and pancreas in non-obese pre-diabetes model mice than in their normal littermates. Subsequently, in the pre-diabetes model mice, Va14-Ja18 was activated with α-galactosylceramide (α-GalCer) and its effect on glucose tolerance was estimated. The simultaneous injection of α-GalCer and lymphocytes improved glucose tolerance with its maximum effect on the 3rd day. An analysis of circulating cytokine levels revealed that interferon-γ, which is a pro-inflammatory cytokine, was secreted only on the 1st day after treatment with α-GalCer and that interleukin (IL)-4, which is an anti-inflammatory cytokine, was secreted from the 1st to the 4th day. The prolonged secretion of IL-4 was thought to substantially contribute to the improvement of glucose tolerance. Based on these results, the functional role of NKT cells in pre-diabetes is to improve metabolic dysfunctions.
KeywordsPre-diabetes model mice NKT cells Adipose tissue Non-obese
This work was supported in part by the Strategic Research Promotion Program of the Ministry of Education, Culture, Sports, Science, and Technology, on the research subject “Development of Next Generation Bioresources”. We appreciate the valuable advice about experimental methodology that we received from Prof. Emer. Hideaki Matsuoka of Tokyo University of Agriculture and Technology. We also thank Kana Kitazumi and Eri Ochiai for their technical support.
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