title: Glypican-4 is increased in human subjects with impaired glucose tolerance and decreased in patients with newly diagnosed type 2 diabetes.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
authors.affiliation: Department of Endocrinology, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400016, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Li
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Xu
authors.forename: Wenjing
authors.initials: W
authors.lastname: Hu
authors.forename: Minyan
authors.initials: M
authors.lastname: Li
authors.forename: Mengliu
authors.initials: M
authors.lastname: Yang
authors.forename: Yaxu
authors.initials: Y
authors.lastname: Wang
authors.forename: Yong
authors.initials: Y
authors.lastname: Luo
authors.forename: Xianxiang
authors.initials: X
authors.lastname: Zhang
authors.forename: Hua
authors.initials: H
authors.lastname: Liu
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.forename: Gangyi
authors.initials: G
authors.lastname: Yang
mesh_terms: D000293:Adolescent; D000328:Adult; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000235:genetics; D015536:Down-Regulation; D005260:Female; D015309:Glucose Clamp Technique; D018149:Glucose Intolerance / Q000097:blood* / Q000235:genetics; D005951:Glucose Tolerance Test; D053673:Glypicans / Q000097:blood* / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D015854:Up-Regulation; D055815:Young Adult
chemical_list: C492044:GPC4 protein, human; D053673:Glypicans