Burn Unit, Department of Surgery, Massachusetts General Hospital, Boston, MA, USA.
Surgery. 2011 May;149(5):635-44. doi: 10.1016/j.surg.2010.11.017. Epub 2011 Feb 5.
Hyperglycemia with insulin resistance is commonly seen in severely burned patients and tight glycemia control with insulin may be beneficial in this condition. The most potent insulinotropic hormone, glucagon-like peptide 1 (GLP-1), stimulates insulin secretion in a glucose-dependent manner. Because infusion of GLP-1 never reduces glucose levels to below ∼70 mg/dL, the risk of hypoglycemia by using insulin is reduced. In this study we investigated the metabolic effects of GLP-1 infusion after burn injury in an animal model.
Male CD rats were divided in 3 groups: burn injury with saline, burn injury with GLP-1 treatment, and sham burn (SB). Burn injury was full thickness 40% total body surface area. The burn injury with GLP-1 treatment group received GLP-1 infusion via osmotic pump. Fasting blood glucose, plasma insulin, and plasma GLP-1 levels were measured during intraperitoneal glucose tolerance tests. Expressions of caspase 3 and bcl-2 were evaluated in pancreatic islets. In a subset of animals, protein metabolism and total energy expenditure were measured.
Fasting GLP-1 was reduced in burn injury with saline compared to SB or burn injury with GLP-1 treatment. Burn injury with GLP-1 treatment showed reduced fasting blood glucose, improved intraperitoneal glucose tolerance test results, with increased plasma insulin and GLP-1 responses to glucose. GLP-1 reduced protein breakdown and total energy expenditure in burn injury with GLP-1 treatment versus burn injury with saline, with improved protein balance. Increased expression of caspase 3 and decreased expression of bcl-2 in islet cells by burn injury were ameliorated by GLP-1.
Burn injury reduced plasma GLP-1 in association with insulin resistance. GLP-1 infusion improved glucose tolerance and showed anabolic effects on protein metabolism and reduced total energy expenditure after burn injury, possibly via insulinotropic and non insulinotropic mechanisms.
严重烧伤患者常伴有高血糖和胰岛素抵抗，用胰岛素严格控制血糖可能对此有益。最有效的胰岛素促分泌激素胰高血糖素样肽 1（GLP-1）以葡萄糖依赖的方式刺激胰岛素分泌。由于 GLP-1 的输注从未将血糖水平降低到 70mg/dL 以下，因此使用胰岛素降低低血糖的风险。在这项研究中，我们在动物模型中研究了烧伤后 GLP-1 输注的代谢效应。
雄性 CD 大鼠分为 3 组：盐水烧伤组、GLP-1 治疗烧伤组和假烧伤（SB）组。烧伤面积为 40%的全身体表面积。GLP-1 治疗烧伤组通过渗透泵输注 GLP-1。在腹腔葡萄糖耐量试验期间测量空腹血糖、血浆胰岛素和 GLP-1 水平。评估胰岛细胞中 caspase 3 和 bcl-2 的表达。在部分动物中，测量蛋白质代谢和总能量消耗。
与 SB 或 GLP-1 治疗烧伤相比，盐水烧伤后 GLP-1 降低。GLP-1 治疗烧伤显示空腹血糖降低，腹腔葡萄糖耐量试验结果改善，同时增加了血浆胰岛素和 GLP-1 对葡萄糖的反应。与盐水烧伤相比，GLP-1 降低了 GLP-1 治疗烧伤的蛋白质分解和总能量消耗，改善了蛋白质平衡。GLP-1 减轻了烧伤引起的胰岛细胞中 caspase 3 表达增加和 bcl-2 表达减少。
烧伤导致血浆 GLP-1 降低，与胰岛素抵抗有关。GLP-1 输注改善了葡萄糖耐量，并对烧伤后的蛋白质代谢产生合成代谢作用，降低了总能量消耗，可能通过胰岛素依赖和非胰岛素依赖机制。
