Yamashita Hayato, Ishikawa Michiko, Inoue Taketo, Usami Makoto, Usami Yu, Kotani Joji
*Department of Biophysics, Kobe University Graduate School of Health Sciences, Hyogo, Japan †Department of Emergency, Disaster and Critical Care Medicine, Hyogo College of Medicine, Hyogo, Japan ‡Division of Orthopedic Surgery, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Shock. 2017 Apr;47(4):455-462. doi: 10.1097/SHK.0000000000000747.
Dysregulation of glucose metabolism, including hyperglycemia with insulin resistance, is commonly observed in critically ill patients. Interleukin-18 (IL-18) improves the insulin resistance associated with obesity, but the relationship between IL-18 and glucose metabolism in sepsis was unclear. The purpose of this study was to investigate the influence of IL-18 on hyperglycemia during sepsis.
Sepsis was induced using cecal ligation and puncture (CLP) in wild-type (WT) mice, IL-18 knockout (KO) mice, and IL-18 KO mice pretreated with recombinant IL-18. Blood glucose and plasma insulin, glucagon, and corticosterone were measured. The mRNAs for gluconeogenic enzymes (g6pc, pck1) and activation of insulin signaling were also analyzed.
In both WT and IL-18 KO mice, CLP operation led to hyperglycemia that lasted longer (18 h) than after sham operation (6 h). Blood glucose levels in IL-18 KO mice were significantly higher than in WT mice, without alteration of insulin or glucagon levels. In IL-18 KO mice, insulin signaling in the liver and skeletal muscle was decreased during hyperglycemia as compared with WT mice without suppression of hepatic glucose production enzymes. Pretreatment with recombinant IL-18 reduced blood glucose levels after CLP. Additionally, corticosterone levels were higher after CLP in the presence of either endogenous or exogenous IL-18.
IL-18 may reduce blood glucose by modulating insulin signaling in the liver during sepsis-induced hyperglycemia. IL-18 is an important factor associated with alterations in blood glucose during sepsis.
葡萄糖代谢失调，包括伴有胰岛素抵抗的高血糖，在危重症患者中普遍存在。白细胞介素-18（IL-18）可改善与肥胖相关的胰岛素抵抗，但IL-18与脓毒症时葡萄糖代谢之间的关系尚不清楚。本研究旨在探讨IL-18对脓毒症期间高血糖的影响。
采用盲肠结扎穿刺（CLP）法诱导野生型（WT）小鼠、IL-18基因敲除（KO）小鼠以及经重组IL-18预处理的IL-18 KO小鼠发生脓毒症。检测血糖、血浆胰岛素、胰高血糖素和皮质酮水平。分析糖异生酶（g6pc、pck1）的mRNA以及胰岛素信号通路的激活情况。
在WT小鼠和IL-18 KO小鼠中，CLP手术均导致高血糖，且持续时间（18小时）长于假手术（6小时）。IL-18 KO小鼠的血糖水平显著高于WT小鼠，而胰岛素或胰高血糖素水平无变化。与WT小鼠相比，IL-18 KO小鼠在高血糖期间肝脏和骨骼肌中的胰岛素信号通路减弱，且肝葡萄糖生成酶未受抑制。重组IL-18预处理可降低CLP术后的血糖水平。此外，在内源性或外源性IL-18存在的情况下，CLP术后皮质酮水平均升高。
IL-18可能通过调节脓毒症诱导的高血糖期间肝脏中的胰岛素信号通路来降低血糖。IL-18是脓毒症期间血糖变化的一个重要相关因素。
