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囊性纤维化伴或不伴糖尿病患者中活性 GLP-1 水平降低。

Reduced levels of active GLP-1 in patients with cystic fibrosis with and without diabetes mellitus.

机构信息

Department of Clinical Sciences, Biomedical Center, Lund University, Sweden.

出版信息

J Cyst Fibros. 2012 Mar;11(2):144-9. doi: 10.1016/j.jcf.2011.11.001. Epub 2011 Dec 3.

DOI:10.1016/j.jcf.2011.11.001
PMID:22138561
Abstract

Glucagon like peptide 1 (GLP-1) is an incretin hormone released as a bioactive peptide from intestinal L-cells in response to eating. It acts on target cells and exerts several functions as stimulating insulin and inhibiting glucagon. It is quickly deactivated by the serine protease dipeptidyl peptidase IV (DPP-IV) as an important regulatory mechanism. GLP-1 analogues are used as antidiabetic drugs in patients with type 2 diabetes. We served patients with cystic fibrosis (CF, n=29), cystic fibrosis related diabetes (CFRD, n=19) and healthy controls (n=18) a standardized breakfast (23 g protein, 25 g fat and 76 g carbohydrates) after an overnight fasting. Blood samples were collected before meal as well as 15, 30, 45 and 60 min after the meal in tubes prefilled with a DPP-IV inhibitor. The aim of the study was to compare levels of GLP-1 in patients with CF, CFRD and in healthy controls. We found that active GLP-1 was significantly decreased in patients with CF and CFRD compared to in healthy controls (p<0.01). However, levels in patients with CFRD tended to be lower but were not significantly lower than in patients with CF without diabetes (p=0.06). Total GLP-1 did not differ between the groups, which points to that the inactive form of GLP-1 is more pronounced in CF patients. The endogenous insulin production (measured by C-peptide) was significantly lower in patients with CFRD as expected. However, levels in non-diabetic CF patients did not differ from the controls. We suggest that the decreased levels of GLP-1 could affect the progression toward CFRD and that more studies need to be performed in order to evaluate a possible treatment with GLP-1 analogues in CF-patients.

摘要

胰高血糖素样肽 1(GLP-1)是一种肠 L 细胞在进食时作为生物活性肽释放的肠促胰岛素激素。它作用于靶细胞并发挥多种功能,如刺激胰岛素和抑制胰高血糖素。它作为一种重要的调节机制,被丝氨酸蛋白酶二肽基肽酶 IV(DPP-IV)迅速失活。GLP-1 类似物被用作 2 型糖尿病患者的抗糖尿病药物。我们给 29 例囊性纤维化(CF)患者、19 例囊性纤维化相关糖尿病(CFRD)患者和 18 例健康对照者(n=18)服用了标准早餐(23 克蛋白质、25 克脂肪和 76 克碳水化合物),禁食一夜后。在餐前行空腹采血,以及在用 DPP-IV 抑制剂预填充的采血管中采血 15、30、45 和 60 分钟后采血。该研究的目的是比较 CF、CFRD 患者和健康对照组患者的 GLP-1 水平。我们发现,与健康对照组相比,CF 和 CFRD 患者的活性 GLP-1 明显降低(p<0.01)。然而,CFRD 患者的水平较低,但与无糖尿病的 CF 患者相比没有显著降低(p=0.06)。各组之间的总 GLP-1 无差异,这表明 CF 患者的无活性 GLP-1 更为明显。预期 CFRD 患者的内源性胰岛素分泌(通过 C 肽测量)明显降低。然而,非糖尿病 CF 患者的水平与对照组无差异。我们认为,GLP-1 水平降低可能会影响向 CFRD 的进展,需要进行更多的研究,以评估在 CF 患者中使用 GLP-1 类似物的可能治疗方法。

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