Nowak Natalia, Hohendorff Jerzy, Solecka Iwona, Szopa Magdalena, Skupien Jan, Kiec-Wilk Beata, Mlynarski Wojciech, Malecki Maciej T
Department of Metabolic Diseases, Jagiellonian University Medical College, 15 Kopernika Street, 31-501, Krakow, Poland.
Section on Genetics and Epidemiology, Joslin Diabetes Center, Boston, MA, USA.
Endocrine. 2015 Dec;50(3):643-9. doi: 10.1007/s12020-015-0627-5. Epub 2015 May 19.
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.
胃饥饿素是一种调节食欲的激素。它可能参与了不同类型糖尿病的病理生理过程。在动物研究中，胃饥饿素的表达受肝细胞核因子1α（HNF1A）调控。HNF1A基因突变会导致青年发病的成年型糖尿病（MODY）。我们旨在评估HNF1A-MODY患者及其他类型糖尿病患者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名携带HNF1A基因突变的糖尿病患者、55名2型糖尿病（T2DM）患者、42名1型糖尿病（T1DM）患者、31名携带糖尿病相关葡萄糖激酶（GCK）基因突变的患者以及51名健康对照者。使用针对其酰化和去酰化形式C末端片段的多克隆抗体通过免疫酶测定法测量血浆胃饥饿素浓度。HNF1A-MODY患者、GCK-MODY患者、T1DM患者和T2DM患者的胃饥饿素浓度分别为0.75±0.32、0.70±0.21、0.50±0.20和0.40±0.16 ng/ml。HNF1A-MODY和GCK-MODY患者的胃饥饿素水平高于T1DM和T2DM患者（所有比较p<0.001），但低于非糖尿病对照者（1.02±0.29 ng/ml，两个比较均p<0.001）。在多变量线性模型中，两种MODY组与常见糖尿病类型之间的差异仍然显著。按HNF1A突变类型分析表明，不同类型序列差异患者的胃饥饿素浓度相似。HNF1A-MODY和GCK-MODY患者的血浆胃饥饿素水平高于常见的多基因形式糖尿病患者。
