Fibroblast growth factor 21 prevents glycemic deterioration in insulin deficient mouse models of diabetes
Fibroblast growth factor 21 prevents glycemic deterioration in insulin deficient mouse models of diabetes
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DOI：
10.1016/j.ejphar.2015.07.003
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发表时间：
2015-10-05
影响因子：
5
通讯作者：
Ahren, Bo
中科院分区：
文献类型：
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作者：
Andersen, Birgitte;Omar, Bilal A.;Ahren, Bo
在1型糖尿病中，在疾病发作后立即迅速失去血糖控制。本研究旨在探讨重组成纤维细胞生长因子21（FGF 21）是否能减轻胰岛素缺乏型糖尿病早期血糖控制的恶化。随机接受每日两次皮下注射载体或重组人FGF 21，剂量为0.3和1.0 mg/kg，持续10天。每天记录体重，并在随机化后6天和10天测定5小时空腹血糖、胰岛素、胰高血糖素、游离脂肪酸和酮。相比之下，在1.0 mg/kg BID时，FGF 21不能阻止STZ后血糖的升高。在研究结束时，用FGF 21 1.0 mg/kg BID治疗的糖尿病组中的血浆胰高血糖素显著高于未治疗组。这在用FGF 21 0.3mg/kg BID治疗的组中未观察到。FGF 21治疗的血浆游离脂肪酸存在显著的剂量依赖性降低，但血浆酮（β-羟丁酸酯）无显著变化。总之，FGF 21可防止胰岛素缺乏型糖尿病小鼠模型中胰高血糖素增加，并具有降脂特性，尽管通过增加剂量可观察到胰高血糖素水平增加，且高血糖症持续存在。(C)2015爱思唯尔B. V.保留所有权利。
In type 1 diabetes, there is a rapid loss of glycemic control immediately after onset of the disease. We aimed to determine if the deterioration of glycemic control that occurs early after the onset of insulin-deficient diabetes could be blunted by treatment with recombinant fibroblast growth factor 21 (FGF21).Normal C57BL/6J mice made diabetic by a single high dose injection of streptozotocin (STZ) were randomized to receive twice daily subcutaneous injection of vehicle or recombinant human FGF21 at doses of 0.3 and 1.0 mg/kg for 10 days. Body weight was recorded daily and 5 h fasted glucose, insulin, glucagon, free fatty acids and ketones were determined at 6 and 10 days post-randomization.The increase in fasting plasma glucose induced by STZ in untreated mice was prevented with FGF21 at 0.3 mg/kg BID. In contrast, at 1.0 mg/kg BID, FGF21 did not prevent the rise in plasma glucose after STZ. At the end of the study, plasma glucagon was significantly higher in the diabetic group treated with FGF21 1.0 mg/kg BID than in the untreated group. This was not seen for the group treated with FGF21 0.3 mg/kg BID. There were significant dose dependent reductions in plasma free fatty acids with FGF21 treatment but no significant change in plasma ketones (beta-hyclroxybutyrate). FGF21 treatment did not have significant effects on body weight in lean insulin deficient mice.In conclusion, FGF21 prevents increases in glycaemia and has lipid lowering properties in mouse models of insulin deficient diabetes, although by increasing the dose increased glucagon levels are seen and hyperglycemia persists. (C) 2015 Elsevier B.V. All rights reserved.