List E O, Palmer A J, Berryman D E, Bower B, Kelder B, Kopchick J J
Edison Biotechnology Institute, Ohio University, 101 Konneker Research Laboratories, Athens, OH 45701, USA.
Diabetologia. 2009 Aug;52(8):1647-55. doi: 10.1007/s00125-009-1402-z. Epub 2009 May 26.
AIMS/HYPOTHESIS: Growth hormone has been used experimentally in two studies to treat individuals with type 2 diabetes, with both reporting beneficial effects on glucose metabolism. However, concerns over potential diabetogenic actions of growth hormone complicate its anticipated use to treat type 2 diabetes. Thus, an animal model of type 2 diabetes could help evaluate the effects of growth hormone for treating this condition.
Male C57BL/6J mice were placed on a high-fat diet to induce obesity and type 2 diabetes. Starting at 16 weeks of age, mice were treated once daily for 6 weeks with one of four different doses of growth hormone. Body weight, body composition, fasting blood glucose, insulin, glucose tolerance, liver triacylglycerol, tissue weights and blood chemistries were determined.
Body composition measurements revealed a dose-dependent decrease in fat and an increase in lean mass. Analysis of fat loss by depot revealed that subcutaneous and mesenteric fat was the most sensitive to growth hormone treatment. In addition, growth hormone treatment resulted in improvement in glucose metabolism, with the highest dose normalising glucose, glucose tolerance and liver triacylglycerol. In contrast, insulin levels were not altered by the treatment, nor did organ weights change. However, fasting plasma leptin and resistin were significantly decreased after growth hormone treatment.
CONCLUSIONS/INTERPRETATION: Growth hormone therapy improves glucose metabolism in this mouse model of obesity and type 2 diabetes, providing a means to explore the molecular mechanism(s) of this treatment.
目的/假设：在两项研究中已对生长激素进行了实验性应用，以治疗2型糖尿病患者，两项研究均报告了其对葡萄糖代谢的有益作用。然而，对生长激素潜在致糖尿病作用的担忧使其用于治疗2型糖尿病的预期应用变得复杂。因此，2型糖尿病动物模型有助于评估生长激素治疗这种疾病的效果。
将雄性C57BL/6J小鼠置于高脂肪饮食中以诱导肥胖和2型糖尿病。从16周龄开始，小鼠每天接受一次治疗，持续6周，使用四种不同剂量的生长激素之一。测定体重、身体成分、空腹血糖、胰岛素、葡萄糖耐量、肝脏三酰甘油、组织重量和血液化学指标。
身体成分测量显示脂肪呈剂量依赖性减少，瘦体重增加。按储存部位分析脂肪减少情况发现，皮下和肠系膜脂肪对生长激素治疗最为敏感。此外，生长激素治疗使葡萄糖代谢得到改善，最高剂量使血糖、葡萄糖耐量和肝脏三酰甘油恢复正常。相比之下，治疗未改变胰岛素水平，器官重量也未改变。然而，生长激素治疗后空腹血浆瘦素和抵抗素显著降低。
结论/解读：生长激素疗法可改善这种肥胖和2型糖尿病小鼠模型的葡萄糖代谢，为探索这种治疗方法的分子机制提供了一种手段。
