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

Acta Diabetol. 2014 Dec;51(6):981-90. doi: 10.1007/s00592-014-0652-5. Epub 2014 Sep 21.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Cohort Studies
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / genetics
  • Down-Regulation
  • Female
  • Glucose Clamp Technique
  • Glucose Intolerance / blood*
  • Glucose Intolerance / genetics
  • Glucose Tolerance Test
  • Glypicans / blood*
  • Glypicans / genetics
  • Humans
  • Male
  • Middle Aged
  • Up-Regulation
  • Young Adult

Substances

  • GPC4 protein, human
  • Glypicans