School of Life Science and Technology, Tokyo Institute of Technology, 4259-B-25 Nagatsuta-cho, Midori-ku, Yokohama, Kanagawa, 226-8501, Japan.
Laboratory of Developmental Genetics, Institute of Resource Development and Analysis, Kumamoto University, Chuo-Ku, Honjo 2-2-1, Kumamoto, 860-0811, Japan; Center for Metabolic Regulation of Healthy Aging, Kumamoto University, Chuo-Ku, Honjo 1-1-1, Kumamoto, 860-8556, Japan.
Biochem Biophys Res Commun. 2023 Oct 30;679:58-65. doi: 10.1016/j.bbrc.2023.08.064. Epub 2023 Aug 30.
The metabolites in the plasma serve as potential biomarkers of disease. We previously established an early-onset diabetes mouse model, Ins2 Kuma mice, under a severe immune-deficient (Rag-2/Jak3 double-deficient in BALB/c) background. Here, we revealed the differences in plasma amino acid profiles between Kuma and the wild-type mice. We observed an early reduction in glucogenic and ketogenic amino acids, a late increase in branched-chain amino acids (BCAAs) and succinyl CoA-related amino acids, and a trend of increasing ketogenic amino acids in Kuma mice than in the wild-type mice. Kuma mice exhibited hyperglucagonemia at high blood glucose, leading to perturbations in plasma amino acid profiles. The reversal of blood glucose by islet transplantation normalized the increases of the BCAAs and several aspects of the altered metabolic profiles in Kuma mice. Our results indicate that the Kuma mice are a unique animal model to study the link between plasma amino acid profile and the progression of diabetes for monitoring the therapeutic effects.
血浆中的代谢物可作为疾病的潜在生物标志物。我们之前在严重免疫缺陷（BALB/c 背景下的 Rag-2/Jak3 双重缺陷）下建立了一种早期发病的糖尿病小鼠模型，Ins2 Kuma 小鼠。在这里，我们揭示了 Kuma 小鼠与野生型小鼠之间血浆氨基酸谱的差异。我们观察到生糖和生酮氨基酸早期减少，支链氨基酸（BCAA）和琥珀酰辅酶 A 相关氨基酸晚期增加，以及 Kuma 小鼠中生酮氨基酸呈增加趋势。Kuma 小鼠在高血糖时表现出高胰高血糖素血症，导致血浆氨基酸谱发生紊乱。胰岛移植逆转血糖水平使 Kuma 小鼠的 BCAAs 增加和代谢谱的几个方面恢复正常。我们的结果表明，Kuma 小鼠是研究血浆氨基酸谱与糖尿病进展之间联系的独特动物模型，可用于监测治疗效果。
