Journal
ACTA DIABETOLOGICA
Volume 51, Issue 6, Pages 981-990Publisher
SPRINGER-VERLAG ITALIA SRL
DOI: 10.1007/s00592-014-0652-5
Keywords
Glypican-4; Insulin resistance; Impaired glucose tolerance; Type 2 diabetes mellitus
Categories
Funding
- National Natural Science Foundation of China [81270913, 81070640, 81100567, 81300702, 81300670]
- Doctoral Fund of Ministry of Education of China [20105503110002, 20125503110003]
- Natural Science Foundation Key Project of CQ cstc [cstc2012 jjB10022]
- CQ cstc [cstc2011jjA10077]
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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 RTPCR 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.
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