Glypican-4 is increased in human subjects with impaired glucose tolerance and decreased in patients with newly diagnosed type 2 diabetes

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• 作者：Ke Li (1)
  Xiaohui Xu (1)
  Wenjing Hu (1)
  Minyan Li (2)
  Mengliu Yang (1)
  Yaxu Wang (3)
  Yong Luo (4)
  Xianxiang Zhang (4)
  Hua Liu (5)
  Ling Li (1)
  Gangyi Yang (1)
  
• 关键词：Glypican ; 4 ; Insulin resistance ; Impaired glucose tolerance ; Type 2 diabetes mellitus
• 刊名：Acta Diabetologica
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：51
• 期：6
• 页码：981-990
• 全文大小：702 KB
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• 作者单位：Ke Li (1)
  Xiaohui Xu (1)
  Wenjing Hu (1)
  Minyan Li (2)
  Mengliu Yang (1)
  Yaxu Wang (3)
  Yong Luo (4)
  Xianxiang Zhang (4)
  Hua Liu (5)
  Ling Li (1)
  Gangyi Yang (1)
  
  1. Department of Endocrinology, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400016, China
  2. Key Laboratory of Diagnostic Medicine (Ministry of Education) and Department of Clinical Biochemistry, College of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, China
  3. Department of Surgery, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400016, China
  4. Department of Endocrinology, Chongqing Three Gorges Central Hospital, Chongqing, 40020, China
  5. Department of Pediatrics, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS, 39216-4505, USA
  
• ISSN：1432-5233

文摘

Context Glypican-4 (GPC-4) has been identified as a novel adipokine capable of enhancing insulin signaling. A significant association between circulating GPC-4 levels and nonalcoholic fatty liver disease and cardiometabolic risk factors has been found in women. Objective The aim of the present study was to investigate the relationship between GPC-4 and insulin resistance in cross-sectional and interventional studies. Patients and design We measured circulating GPC-4 (determined with ELISA) in subjects with NGT, IGT, and nT2DM. Euglycemic-hyperinsulinemic clamps were performed in healthy and T2DM subjects. Real-time RT-PCR and Western blotting were used to assess mRNA and protein expression of GPC-4. Results Circulating GPC-4 levels were significantly higher in IGT subjects and lower in nT2DM subjects compared to controls. Circulating GPC-4 was positively correlated with BMI, WHR, HOMA-IS, and FAT%, while it was inversely correlated with FBG and HbA1c. Excluding diabetic subjects, increasing GPC-4 levels were associated with HOMA-IR and M values. Significantly lower GPC-4 mRNA and protein levels were found in muscle and fat of nT2DM patients, compared to controls. GPC-4 levels were significantly increased upon an oral glucose intake. The secretion of GPC-4 exhibited a characteristic diurnal rhythm in humans, with a major rise occurring between afternoon and midnight. Conclusions Circulating GPC-4 is elevated in prediabetic subjects and is reduced in nT2DM patients. The elevated GPC-4 appears to be associated with insulin resistance and obesity in IGT subjects.