Circulating ghrelin level is higher in HNF1A-MODY and GCK-MODY than in polygenic forms of diabetes mellitus.
Circulating ghrelin level is higher in HNF1A-MODY and GCK-MODY than in polygenic forms of diabetes mellitus.
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DOI：
10.1007/s12020-015-0627-5
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发表时间：
2015-12
期刊：
影响因子：
3.7
通讯作者：
Malecki MT
中科院分区：
文献类型：
--
作者：
Nowak N;Hohendorff J;Solecka I;Szopa M;Skupien J;Kiec-Wilk B;Mlynarski W;Malecki MT
胃饥饿素是一种调节食欲的激素。它可能涉及不同形式糖尿病的病理生理学。在动物研究中，生长素释放肽的表达受到肝细胞核因子 1 α (HNF1A) 的调节。 HNF1A 基因突变会导致青少年发病的成年型糖尿病 (MODY)。我们的目的是评估 HNF1A-MODY 和其他类型糖尿病中的循环胃饥饿素水平，并评估其与 HNF1A 突变状态的关联。我们的队列包括 46 名糖尿病 HNF1A 基因突变携带者、55 名 2 型糖尿病 (T2DM) 受试者、42 名 1 型糖尿病 (T1DM) 患者、31 名葡萄糖激酶 (GCK) 基因突变携带者糖尿病以及 51 名健康对照。使用针对其酰化和去酰化形式的C末端片段的多克隆抗体进行免疫酶测定来测量血浆生长素释放肽浓度。 HNF1A–MODY、GCK–MODY、T1DM 和 T2DM 患者的 Ghrelin 浓度分别为 0.75 ± 0.32、0.70 ± 0.21、0.50 ± 0.20 和 0.40 ± 0.16 ng/ml。 HNF1A–MODY 和 GCK–MODY 中的 ghrelin 水平高于 T1DM 和 T2DM（所有比较的 p < 0.001），但低于非糖尿病对照（1.02 ± 0.29 ng/ml，两个比较的 p < 0.001）。在多元线性模型中，MODY 组和常见糖尿病类型之间的差异仍然显着。 HNF1A突变类型分析表明，不同类型序列差异的患者中生长素释放肽浓度相似。 HNF1A-MODY 和 GCK-MODY 的血浆生长素释放肽水平高于常见的多基因糖尿病。
Ghrelin is a hormone that regulates appetite. It is likely to be involved in the pathophysiology of varying forms of diabetes. In animal studies, the ghrelin expression was regulated by the hepatocyte nuclear factor 1 alpha (HNF1A). Mutations of the HNF1A gene cause maturity onset diabetes of the young (MODY). We aimed to assess the circulating ghrelin levels in HNF1A–MODY and in other types of diabetes and to evaluate its association with HNF1A mutation status. Our cohort included 46 diabetic HNF1A gene mutation carriers, 55 type 2 diabetes (T2DM) subjects, 42 type 1 diabetes (T1DM) patients, and 31 glucokinase (GCK) gene mutation carriers with diabetes as well as 51 healthy controls. Plasma ghrelin concentration was measured using the immunoenzymatic assay with polyclonal antibody against the C-terminal fragment of its acylated and desacylated forms. Ghrelin concentrations were 0.75 ± 0.32, 0.70 ± 0.21, 0.50 ± 0.20, and 0.40 ± 0.16 ng/ml in patients with HNF1A–MODY, GCK–MODY, T1DM, and T2DM, respectively. The ghrelin levels were higher in HNF1A–MODY and GCK–MODY than in T1DM and T2DM (p < 0.001 for all comparisons) but lower than in non-diabetic controls (1.02 ± 0.29 ng/ml, p < 0.001 for both comparisons). In the multivariate linear model, the differences between both MODY groups and common diabetes types remained significant. Analysis by a HNF1A mutation type indicated that ghrelin concentration is similar in patients with different types of sequence differences. Plasma ghrelin level is higher in HNF1A–MODY and GCK–MODY than in the common polygenic forms of diabetes.