Increased circulating levels of betatrophin in individuals with long-standing type 1 diabetes.

Increased circulating levels of betatrophin in individuals with long-standing type 1 diabetes.
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DOI:
10.1007/s00125-013-3071-1
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发表时间:
2014-01
期刊:
影响因子:
8.2
通讯作者:
Carlsson, Per-Ola
Carlsson, Per-Ola
中科院分区:
医学1区
文献类型:
--
作者:
Espes, Daniel;Lau, Joey;Carlsson, Per-Ola

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激素betatrophin最近被描述为小鼠中β细胞增殖的有效刺激剂。胰岛素抵抗,而不是胰岛素缺乏,导致β-营养素表达上调。如果发现这些发现完全适用于人类,这将为未来betatrophin治疗1型糖尿病开辟可能性。本研究首次测量了人体中betatrophin的浓度,并验证了1型糖尿病患者和健康个体之间循环betatrophin浓度没有差异的假设。采用酶联免疫吸附法测定33例1型糖尿病患者和24例年龄匹配的健康对照者血浆β-营养素浓度。研究参与者的特点是血脂,BMI,血糖和HbA 1c,以及糖尿病患者,他们的胰岛素需求和任何残留的C肽浓度。血浆betatrophin浓度通常为300 pg/ml,但在1型糖尿病患者中大约加倍。在患者中,betatrophin与年龄,血脂,BMI,血糖控制或胰岛素需求量之间没有相关性,而在对照组中betatrophin水平随年龄增加而增加。患者和健康对照组的BMI、血压和三酰甘油、LDL-胆固醇和HDL-胆固醇水平相似。与最近在胰岛素缺乏小鼠模型中所描述的相比,1型糖尿病中betatrophin的循环浓度增加。然而,增加的betatrophin浓度不能防止C肽的损失。因此,如果不使用超生理剂量或与免疫调节治疗相结合,1型糖尿病的Betatrophin治疗可能不会成功。
The hormone betatrophin was recently described as a potent stimulator of beta cell proliferation in mice. Insulin resistance, but not insulin deficiency, caused upregulation of betatrophin expression. If these findings were found to be fully applicable in humans, this would open up the possibility of future betatrophin treatment in type 1 diabetes. The present study measured for the first time betatrophin concentrations in humans and tested the hypothesis that there would be no difference in circulating betatrophin concentrations between patients with type 1 diabetes and healthy individuals. Betatrophin concentrations in plasma of 33 patients with type 1 diabetes and 24 age-matched healthy controls were measured by ELISA. The study participants were characterised for blood lipids, BMI, plasma glucose and HbA1c, and, for the diabetic patients, their insulin requirements and any residual C-peptide concentrations. Plasma betatrophin concentrations were normally ∼300 pg/ml, but were approximately doubled in patients with type 1 diabetes. In the patients, there were no correlations between betatrophin and age, blood lipids, BMI, glucose control or insulin requirement, whereas in controls betatrophin levels increased with age. BMI, blood pressure and triacylglycerol, LDL-cholesterol and HDL-cholesterol levels were similar in patients and healthy controls. Circulating concentrations of betatrophin are increased in type 1 diabetes in contrast with what was recently described in an insulin-deficient mouse model. However, increased betatrophin concentrations do not protect against loss of C-peptide. Betatrophin treatment in type 1 diabetes would therefore probably not be successful without the use of supraphysiological doses or a combination with immune regulatory treatment.
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