title: Zinc-α2-glycoprotein is associated with insulin resistance in humans and is regulated by hyperglycemia, hyperinsulinemia, or liraglutide administration: cross-sectional and interventional studies in normal subjects, insulin-resistant subjects, and subjects with newly diagnosed diabetes.
abstract: OBJECTIVE
  Zinc-α2-glycoprotein (ZAG) has been proposed to play a role in the pathogenesis of insulin resistance. Previous studies in humans and in rodents have produced conflicting results regarding the link between ZAG and insulin resistance. The objective of this study was to examine the relationships between ZAG and insulin resistance in cross-sectional and interventional studies.
  
  
  METHODS
  Serum ZAG (determined with ELISA) was compared with various parameters related to insulin resistance in subjects with normal glucose tolerance, impaired glucose tolerance (IGT), and newly diagnosed type 2 diabetes mellitus (T2DM), and in women with or without polycystic ovary syndrome (PCOS). Euglycemic-hyperinsulinemic clamps were performed in healthy and PCOS women. Real-time RT-PCR and Western blotting were used to assess mRNA and protein expression of ZAG. The effect of a glucagon-like peptide-1 agonist on ZAG was studied in a 12-week liraglutide treatment trial.
  
  
  RESULTS
  Circulating ZAG was lower in patients with IGT and newly diagnosed T2DM than in controls. Circulating ZAG correlated positively with HDL cholesterol and adiponectin, and correlated inversely with BMI, waist-to-hip ratio, body fat percentage, triglycerides, fasting blood glucose, fasting insulin, HbA1c, and homeostasis model assessment of insulin resistance (HOMA-IR). On multivariate analysis, ZAG was independently associated with BMI, HOMA-IR, and adiponectin. ZAG mRNA and protein were decreased in adipose tissue of T2DM patients. Moreover, circulating ZAG levels were lower in women with PCOS than in women with high insulin sensitivity. Liraglutide treatment for 12 weeks significantly increased circulating ZAG levels.
  
  
  CONCLUSIONS
  We conclude that ZAG may be an adipokine associated with insulin resistance.
authors.affiliation: Department of Endocrinology, Chongqing Medical University, Chongqing,China.
authors.forename: Mengliu
authors.initials: M
authors.lastname: Yang
authors.forename: Rui
authors.initials: R
authors.lastname: Liu
authors.forename: Shu
authors.initials: S
authors.lastname: Li
authors.forename: Yu
authors.initials: Y
authors.lastname: Luo
authors.forename: Yali
authors.initials: Y
authors.lastname: Zhang
authors.forename: Lili
authors.initials: L
authors.lastname: Zhang
authors.forename: Dongfang
authors.initials: D
authors.lastname: Liu
authors.forename: Yaxu
authors.initials: Y
authors.lastname: Wang
authors.forename: Zhengai
authors.initials: Z
authors.lastname: Xiong
authors.forename: Guenther
authors.initials: G
authors.lastname: Boden
authors.forename: Shirong
authors.initials: S
authors.lastname: Chen
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.forename: Gangyi
authors.initials: G
authors.lastname: Yang
mesh_terms: D054392:Adipokines / Q000097:blood; D000328:Adult; D000368:Aged; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000378:metabolism*; D006946:Hyperinsulinism / Q000097:blood / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology*; D000069450:Liraglutide; D008297:Male; D008875:Middle Aged; D011085:Polycystic Ovary Syndrome; D029589:Seminal Plasma Proteins / Q000378:metabolism*; D000090203:Zn-Alpha-2-Glycoprotein
chemical_list: D054392:Adipokines; D029589:Seminal Plasma Proteins; D000090203:Zn-Alpha-2-Glycoprotein; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1