论文标题
胰岛素刺激的葡萄糖利用受损与高胰岛素 - 渗透性夹具在小鼠肌肉中燃烧诱导的胰岛素耐药性有关
Impairment of insulin-stimulated glucose utilization is associated with burn-induced insulin resistance in mouse muscle by hyperinsulinemic-isoglycemic clamp
论文作者
论文摘要
燃烧引起的胰岛素抵抗与发病率和死亡率的增加有关。然而，在啮齿动物模型中，烧伤损伤对组织特异性胰岛素敏感性及其分子机制的影响仍然未知。这项研究旨在表征在胰岛素夹条件下具有组织特异性胰岛素耐药性的燃烧小鼠模型。 C57BL6/J小鼠遭受了30％的全厚性烧伤损伤，并结合了高胰岛素血糖血糖室（HIC）和正电子发射断层扫描（PET）。肝葡萄糖产生（HGP）和外周葡萄糖消失率（RD）在受伤后7天的不同时间点测量。燃烧的小鼠在燃烧后（PBD）3和7中表现出明显的空腹低血糖和低胰岛素血症（p <0.01），以及能量消耗明显更高（p <0.01）。 HICON PBD 3表明，烧伤诱导的全身胰岛素抵抗，这是由于胰岛素刺激的RD的显着降低（33.0 +/- 10.2 vs 68.3 +/- 5.9 mg/kg/kg/min; p <0.05）。相比之下，在基底和夹具时期，燃烧和假小鼠的HGP都相当。与假燃烧的小鼠相比，PBD 3上的PET显示出胰岛素刺激的18F标记的2-氟-2-脱氧-D-葡萄糖的摄取，燃烧小鼠的股四头肌吸收。在PBD 3上从燃烧的小鼠中收获的甲壳虫肌肉显示，胰岛素刺激的酪氨酸磷酸化减少了胰岛素受体底物-1至34.7％的胰岛素磷酸化，通过免疫印迹分析（p <0.05），在假燃烧小鼠中的胰岛素磷酸化降低了。这些发现表明，骨骼肌中胰岛素刺激的RD受损（未升高HGP）在小鼠模型中燃烧诱导的胰岛素耐药性的发展中起作用。
Burn-induced insulin resistance is associated with increased morbidity and mortality; however, the impact of burn injury on tissue-specific insulin sensitivity and its molecular mechanisms with consideration of insulin state remains unknown in rodent models. This study was designed to characterize a burn mouse model with tissue-specific insulin resistance under insulin clamp conditions. C57BL6/J mice were subjected to 30% full-thickness burn injury and underwent the combination of hyperinsulinemic isoglycemicclamp (HIC) and positron emission tomography (PET). Hepatic glucose production (HGP) and peripheral glucose disappearance rate (Rd) were measured at different time points up to 7 days post injury. Burned mice showed a significant fasting hypoglycemia and hypoinsulinemia (P < 0.01) on post-burn day (PBD) 3 and 7 along with significantly higher energy expenditure (P < 0.01). HICon PBD 3 demonstrated that burn injury induced systemic insulin resistance, resulting from a significant decrease in insulin-stimulated Rd (33.0 +/- 10.2 vs 68.3 +/- 5.9 mg/kg/min; P < 0.05). In contrast, HGP of burned and sham mice was comparable both in the basal and clamp period. PET on PBD 3 showed a lower insulin-stimulated 18F-labeled 2-fluoro-2-deoxy-D-glucose uptake in the quadriceps of burned mice compared with sham-burned mice. Gastrocnemius muscle harvested from burned mice on PBD 3 showed decreased insulin-stimulated tyrosine phosphorylation of insulin receptor substrate-1 to 34.7% of that in sham-burn mice by immunoblotting analysis (P < 0.05). These findings suggest that impaired insulin-stimulated Rd in skeletal muscle, not elevated HGP, plays a role in the development of burn-induced insulin resistance in a mouse model.
