Laboratory of Synaptic Development and Plasticity, Institute of Life Science & School of Life Sciences, Nanchang University, Nanchang, China.
Department of Biology, Senior Middle School of Yongfeng, Ji'an, China.
Front Endocrinol (Lausanne). 2021 Oct 8;12:770145. doi: 10.3389/fendo.2021.770145. eCollection 2021.
Schizophrenia (SCZ) is a severe psychiatric disease affected by genetic factors and environmental contributors, and premorbid abnormality of glucose metabolism is one of the SCZ characteristics supposed to contribute to the disease's pathological process. Transmembrane protein 108 () is a susceptible gene associated with multiple psychiatric diseases, including SCZ. Moreover, mutant mice exhibit SCZ-like behaviors in the measurement of sensorimotor gating. However, it is unknown whether regulates glucose metabolism homeostasis while it involves SCZ pathophysiological process.
In this research, we found that mutant mice exhibited glucose intolerance, insulin resistance, and disturbed metabolic homeostasis. Food and oxygen consumption decreased, and urine production increased, accompanied by weak fatigue resistance in the mutant mice. Simultaneously, the glucose metabolic pathway was enhanced, and lipid metabolism decreased in the mutant mice, consistent with the elevated respiratory exchange ratio (RER). Furthermore, metformin attenuated plasma glucose levels and improved sensorimotor gating in mutant mice.
Hyperglycemia occurs more often in SCZ patients than in control, implying that these two diseases share common biological mechanisms, here we demonstrate that the mutant may represent such a comorbid mechanism.
精神分裂症（SCZ）是一种受遗传因素和环境因素影响的严重精神疾病，而葡萄糖代谢的前期异常是导致疾病发生的特征之一。跨膜蛋白 108（）是一种与多种精神疾病相关的易感基因，包括 SCZ。此外，突变小鼠在感觉运动门控的测量中表现出 SCZ 样行为。然而，目前尚不清楚在涉及 SCZ 病理生理过程时，是否调节葡萄糖代谢稳态。
在这项研究中，我们发现突变小鼠表现出葡萄糖不耐受、胰岛素抵抗和代谢稳态紊乱。食物和氧气消耗减少，尿液产生增加，同时突变小鼠的疲劳抵抗力减弱。同时，突变小鼠的葡萄糖代谢途径增强，脂质代谢减少，与呼吸交换率（RER）升高一致。此外，二甲双胍可降低突变小鼠的血浆葡萄糖水平并改善其感觉运动门控。
精神分裂症患者比对照组更常出现高血糖，这表明这两种疾病具有共同的生物学机制，我们在此证明突变可能代表了这种共病机制。
