Yoneyama Satoshi, Terashima Hideo, Yamaguchi Ryushiro, Tadano Sosuke, Ohkohchi Nobuhiro
Department of Surgery, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan.
Eur Surg Res. 2015;54(1-2):34-43. doi: 10.1159/000368046. Epub 2014 Oct 14.
In critical illnesses, insulin therapy under overfed conditions with an excessive glucose infusion may cause metabolic disturbances in skeletal muscle mainly through muscle cell glucose uptake and the inhibition of physiological protein breakdown. The aim of this study was to examine the potential negative aspects of insulin therapy in a rat model of sepsis.
Male Sprague-Dawley rats underwent cecal ligation and puncture (CLP) or sham surgery. A pre-established continuous intravenous glucose infusion was initiated immediately after surgery. Rats with sepsis were divided into four groups (n = 7 in each group) based on target blood glucose (BG) levels: a no glucose (NG) group (100-150 mg/dl), moderate glucose (MG) group (200-300 mg/dl), high glucose (HG) group (>300 mg/dl), and the hyperinsulinemia (HI) group, which received the same glucose infusion as the HG group with the insulin infusion (200-300 mg/dl). The sham group underwent sham surgery and received the same glucose infusion as the HG group. All rats were sacrificed 9 h after surgery, and blood samples were collected to measure plasma amino acid (AA) profiles. To examine survival rates in the 48 h following CLP, the HG, MG, and HI groups were newly prepared according to the aforementioned experimental design.
Plasma levels of the branched-chain AAs, glutamine, arginine, citrulline, and alanine among the septic groups slightly and inversely decreased with the amount of glucose infused, and HI had significantly lower values (p < 0.01). A strong correlation was observed among the AAs. Plasma 3-methylhistidine concentrations were the highest in the HI group. The survival rate of the HI group was greater than that of the HG, but did not reach the level of the MG group.
In critical illnesses, insulin therapy under overfed conditions may impair the physiological supply of AAs and conditionally essential AA starvation, such as glutamine and arginine, and may have an adverse impact on the prognosis of patients.
在危重症中，过度喂养且葡萄糖输注过量情况下的胰岛素治疗可能主要通过肌细胞葡萄糖摄取和抑制生理性蛋白质分解而导致骨骼肌代谢紊乱。本研究的目的是在脓毒症大鼠模型中研究胰岛素治疗的潜在负面作用。
雄性Sprague-Dawley大鼠接受盲肠结扎穿刺术（CLP）或假手术。术后立即开始预先设定的持续静脉葡萄糖输注。脓毒症大鼠根据目标血糖（BG）水平分为四组（每组n = 7）：无葡萄糖（NG）组（100 - 150 mg/dl）、中度葡萄糖（MG）组（200 - 300 mg/dl）、高葡萄糖（HG）组（> 300 mg/dl）以及高胰岛素血症（HI）组，该组接受与HG组相同的葡萄糖输注并同时输注胰岛素（200 - 300 mg/dl）。假手术组接受假手术并接受与HG组相同的葡萄糖输注。所有大鼠在术后9小时处死，采集血样以测量血浆氨基酸（AA）谱。为了检测CLP术后48小时的存活率，根据上述实验设计重新制备HG、MG和HI组。
脓毒症组中支链氨基酸、谷氨酰胺、精氨酸、瓜氨酸和丙氨酸的血浆水平随葡萄糖输注量的增加略有下降且呈负相关，HI组的值显著更低（p < 0.01）。氨基酸之间存在强相关性。HI组的血浆3 - 甲基组氨酸浓度最高。HI组的存活率高于HG组，但未达到MG组的水平。
在危重症中，过度喂养情况下的胰岛素治疗可能损害氨基酸的生理性供应以及条件必需氨基酸（如谷氨酰胺和精氨酸）的缺乏，并可能对患者的预后产生不利影响。
