Plasma bile acid changes in type 2 diabetes correlated with insulin secretion in two-step hyperglycemic clamp
静脉-口服双重高糖钳夹中2型糖尿病患者血浆胆汁酸变化与胰岛素分泌的相关性
Shujie Wang
Shanghai National Research Centre for Endocrine and Metabolic Diseases, State Key Laboratory of Medical Genomics, Shanghai Institute for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
These authors contributed equally to this work.Search for more papers by this authorYuying Deng
Shanghai National Research Centre for Endocrine and Metabolic Diseases, State Key Laboratory of Medical Genomics, Shanghai Institute for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
These authors contributed equally to this work.Search for more papers by this authorXiaoyan Xie
Shanghai National Research Centre for Endocrine and Metabolic Diseases, State Key Laboratory of Medical Genomics, Shanghai Institute for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
These authors contributed equally to this work.Search for more papers by this authorJing Ma
Department of Endocrinology, Renji Hospital Affiliated to Shanghai Jiao Tong University Medical School, Shanghai, China
These authors contributed equally to this work.Search for more papers by this authorMin Xu
Shanghai National Research Centre for Endocrine and Metabolic Diseases, State Key Laboratory of Medical Genomics, Shanghai Institute for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Search for more papers by this authorXinjie Zhao
Chinese Academy of Sciences Key Laboratory of Separation Science for Analytical Chemistry, National Chromatographic Research and Analysis Centre, Dalian, China
Search for more papers by this authorWeiqiong Gu
Shanghai National Research Centre for Endocrine and Metabolic Diseases, State Key Laboratory of Medical Genomics, Shanghai Institute for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Search for more papers by this authorJie Hong
Shanghai National Research Centre for Endocrine and Metabolic Diseases, State Key Laboratory of Medical Genomics, Shanghai Institute for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Search for more papers by this authorWeiqing Wang
Shanghai National Research Centre for Endocrine and Metabolic Diseases, State Key Laboratory of Medical Genomics, Shanghai Institute for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Search for more papers by this authorGuowang Xu
Chinese Academy of Sciences Key Laboratory of Separation Science for Analytical Chemistry, National Chromatographic Research and Analysis Centre, Dalian, China
Search for more papers by this authorGuang Ning
Shanghai National Research Centre for Endocrine and Metabolic Diseases, State Key Laboratory of Medical Genomics, Shanghai Institute for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Search for more papers by this authorCorresponding Author
Yanyun Gu
Shanghai National Research Centre for Endocrine and Metabolic Diseases, State Key Laboratory of Medical Genomics, Shanghai Institute for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Correspondence
Yanyun Gu, Shanghai Institute for Endocrine and Metabolic Diseases, 33rd Bldg, 197 RuiJin Er Road, Shanghai 200025, China.
Tel: +86 21 6437 0045 extn 610907
Fax: +86-21-64749885
Email: [email protected]
Yifei Zhang, Department of Endocrinology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 10th Bldg, 197 RuiJin Er Road, Shanghai 200 025, China.
Tel: +86 21 6437 0045 extn 671801
Fax: +86 21 6437 3514
Email: [email protected]
Search for more papers by this authorCorresponding Author
Yifei Zhang
Shanghai National Research Centre for Endocrine and Metabolic Diseases, State Key Laboratory of Medical Genomics, Shanghai Institute for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Correspondence
Yanyun Gu, Shanghai Institute for Endocrine and Metabolic Diseases, 33rd Bldg, 197 RuiJin Er Road, Shanghai 200025, China.
Tel: +86 21 6437 0045 extn 610907
Fax: +86-21-64749885
Email: [email protected]
Yifei Zhang, Department of Endocrinology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 10th Bldg, 197 RuiJin Er Road, Shanghai 200 025, China.
Tel: +86 21 6437 0045 extn 671801
Fax: +86 21 6437 3514
Email: [email protected]
Search for more papers by this authorShujie Wang
Shanghai National Research Centre for Endocrine and Metabolic Diseases, State Key Laboratory of Medical Genomics, Shanghai Institute for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
These authors contributed equally to this work.Search for more papers by this authorYuying Deng
Shanghai National Research Centre for Endocrine and Metabolic Diseases, State Key Laboratory of Medical Genomics, Shanghai Institute for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
These authors contributed equally to this work.Search for more papers by this authorXiaoyan Xie
Shanghai National Research Centre for Endocrine and Metabolic Diseases, State Key Laboratory of Medical Genomics, Shanghai Institute for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
These authors contributed equally to this work.Search for more papers by this authorJing Ma
Department of Endocrinology, Renji Hospital Affiliated to Shanghai Jiao Tong University Medical School, Shanghai, China
These authors contributed equally to this work.Search for more papers by this authorMin Xu
Shanghai National Research Centre for Endocrine and Metabolic Diseases, State Key Laboratory of Medical Genomics, Shanghai Institute for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Search for more papers by this authorXinjie Zhao
Chinese Academy of Sciences Key Laboratory of Separation Science for Analytical Chemistry, National Chromatographic Research and Analysis Centre, Dalian, China
Search for more papers by this authorWeiqiong Gu
Shanghai National Research Centre for Endocrine and Metabolic Diseases, State Key Laboratory of Medical Genomics, Shanghai Institute for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Search for more papers by this authorJie Hong
Shanghai National Research Centre for Endocrine and Metabolic Diseases, State Key Laboratory of Medical Genomics, Shanghai Institute for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Search for more papers by this authorWeiqing Wang
Shanghai National Research Centre for Endocrine and Metabolic Diseases, State Key Laboratory of Medical Genomics, Shanghai Institute for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Search for more papers by this authorGuowang Xu
Chinese Academy of Sciences Key Laboratory of Separation Science for Analytical Chemistry, National Chromatographic Research and Analysis Centre, Dalian, China
Search for more papers by this authorGuang Ning
Shanghai National Research Centre for Endocrine and Metabolic Diseases, State Key Laboratory of Medical Genomics, Shanghai Institute for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Search for more papers by this authorCorresponding Author
Yanyun Gu
Shanghai National Research Centre for Endocrine and Metabolic Diseases, State Key Laboratory of Medical Genomics, Shanghai Institute for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Correspondence
Yanyun Gu, Shanghai Institute for Endocrine and Metabolic Diseases, 33rd Bldg, 197 RuiJin Er Road, Shanghai 200025, China.
Tel: +86 21 6437 0045 extn 610907
Fax: +86-21-64749885
Email: [email protected]
Yifei Zhang, Department of Endocrinology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 10th Bldg, 197 RuiJin Er Road, Shanghai 200 025, China.
Tel: +86 21 6437 0045 extn 671801
Fax: +86 21 6437 3514
Email: [email protected]
Search for more papers by this authorCorresponding Author
Yifei Zhang
Shanghai National Research Centre for Endocrine and Metabolic Diseases, State Key Laboratory of Medical Genomics, Shanghai Institute for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Correspondence
Yanyun Gu, Shanghai Institute for Endocrine and Metabolic Diseases, 33rd Bldg, 197 RuiJin Er Road, Shanghai 200025, China.
Tel: +86 21 6437 0045 extn 610907
Fax: +86-21-64749885
Email: [email protected]
Yifei Zhang, Department of Endocrinology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 10th Bldg, 197 RuiJin Er Road, Shanghai 200 025, China.
Tel: +86 21 6437 0045 extn 671801
Fax: +86 21 6437 3514
Email: [email protected]
Search for more papers by this authorAbstract
enBackground
Bile acids (BAs) conduct crucial signals in human metabolism. Correlations between changes in plasma BA concentrations, insulin secretion defects, and progression of type 2 diabetes mellitus (T2DM) in humans have not been sufficiently investigated. This study explored the trajectories of changes in human plasma BA concentrations and their association with insulin secretion dynamics during a two-step hyperglycemic clamp.
Methods
Eleven healthy subjects with normal glucose tolerance (NGT) and 33 drug-naïve T2DM subjects were enrolled in the study. The two-step hyperglycemic clamp consisted of a classic clamp as Step 1 with fasting, followed by a Step 2 clamp after ingestion of a carbohydrate meal, illustrating basal and incretin-amplified insulin responses to glucose. Plasma BA were assayed using liquid chromatography–tandem mass spectrometry. Nine T2DM subjects were followed-up, and the two-step clamp was repeated after 3 months sulfonylurea treatment.
Results
Ursodeoxycholic acid (UDCA) was lower and lithocholic acid (LCA) and taurocholic acid (TCA) were higher in T2DM compared with NGT subjects. The dynamics of plasma UDCA concentrations and the UDCA/LCA ratio was positively correlated with insulin secretion in T2DM subjects and were corrected after treatment. Moreover, fasting ratios of UDCA/LCA and unconjugated/conjugated BAs were correlated with the first phase of insulin secretion in T2DM subjects.
Conclusion
The abnormal BA composition in T2DM subjects and its correlation with insulin secretion during the clamp suggest an interaction between BA signals and insulin secretion capacity, and the potential to use fasting plasma BA composition indices to predict and evaluate the progression and prognosis of T2DM.
Abstract
zh摘要
背景
胆汁酸在人体代谢中发挥着重要的信号调节作用, 但人体血浆中胆汁酸浓度及胰岛素分泌缺陷与2型糖尿病(T2DM)发展的相关性尚未明确。本研究通过双重高糖钳夹模型探究血浆中胆汁酸浓度改变的轨迹与胰岛素分泌动力学之间的关系。
方法
本研究入组33例初发T2DM患者与11例糖耐量正常的对照者, 运用“静脉-口服双重高糖钳夹试验”模型, 其中第一步为禁食, 第二步为摄取碳水化合物食物, 用来反映基线以及在肠促胰岛素的扩大作用下胰岛素对葡萄糖的应答。利用液相色谱技术检测血浆中胆汁酸浓度。其中9名T2DM患者在给予3个月格列吡嗪治疗后再次进行双糖钳夹试验。
结果
与NGT对照组相比,T2DM受试者中熊去氧胆酸(Ursodeoxycholic acid,UDCA)含量明显降低, 而石胆酸(lithocholic acid,LCA)和牛磺酸结合胆酸(taurocholic acid,TCA)含量明显升高,UDCA浓度的变化和UDCA与LCA的比值与T2DM受试者的胰岛素分泌呈现正相关, 其中UDCA、TCA、LCA在T2DM受试者中的变化在治疗后得到恢复。并且空腹血浆中未结合与结合胆汁酸的比值以及UDCA与LCA的比值与口服和静脉阶段一相胰岛素分泌相关。
结论
本研究通过双重高糖钳夹试验观察到T2DM患者中胆汁酸成分的异常及其与胰岛素分泌的相关性, 提示了胆汁酸信号通路与胰岛素分泌功能可能存在交互作用, 以及利用空腹血浆中的胆汁酸成分预测和评价T2DM进展和预后的可能性。
Supporting Information
| Filename | Description |
|---|---|
| jdb12769-sup-0001-suppinfo.docxWord 2007 document , 592 KB |
File S1. Inclusion and exclusion criteria. Table S1. Area under the curve values of plasma bile acids at different phases of the clamp. Figure S1. Dynamic changes in serum insulin and C-peptide concentrations during the two-step hyperglycemic clamp before and after treatment in type 2 diabetes mellitus (T2DM) subjects. Figure S2. Dynamic changes in total bile acids (BAs) and BA composition during the two-step hyperglycemic clamp after treatment in T2DM subjects. Figure S3. Plasma concentrations of different bile acids during the two-step hyperglycemic clamp before and after treatment in T2DM subjects. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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