Associations between pigment epithelium-derived factor, insulin resistance and high density lipoprotein.

Abstract

AIMS:

To measure serum pigment epithelium-derived factor in control subjects with normal fasting glucose, and in subjects with impaired fasting glucose and those with newly diagnosed Type 2 diabetes, before treatment initiation, and to measure pigment epithelium-derived factor prospectively in patients being treated with HDL-raising therapy, niacin.

METHODS:

We enrolled 89 individuals attending an institutional health screen. Biochemical indices including lipids, homeostasis model assessment-insulin resistance, high-sensitivity C-reactive protein and pigment epithelium-derived factor were analysed in fasting blood. To validate the association between HDL and pigment epithelium-derived factor, we analysed samples from a separate study cohort with low HDL, followed up for 12-weeks while on niacin treatment. Secreted pigment epithelium-derived factor from 3T3-L1 adipocytes, after HDL treatment (24-h), was measured using Western blot analysis.

RESULTS:

Mean (± sd) serum pigment epithelium-derived factor was significantly higher in subjects with impaired fasting glucose [13.99 (± 3.06) μg/ml] and Type 2 diabetes [12.94 (± 2.61)] μg/ml, compared with control subjects [11.83 (± 2.85) μg/ml (P = 0.014)]. In multivariate analyses, serum pigment epithelium-derived factor concentration was associated with BMI (β = 0.32, 0.007), homeostasis model assessment-insulin resistance (β = 0.33, P = 0.01) and HDL (β = -0.24, P = 0.05), after adjustment for age, gender and high-sensitivity C-reactive protein. In the niacin study, on-treatment HDL was an independent determinant of pigment epithelium-derived factor (β = -0.439, P = 0.033), after adjusting for age, homeostasis model assessment-insulin resistance and treatment. Adipocytes treated with HDL were found to have reduced pigment epithelium-derived factor secretion [24.8% (50 μg/ml), 28.4% (100 μg/ml) HDL; P < 0.05)], compared with the control samples.

CONCLUSION:

Serum pigment epithelium-derived factor is positively associated with homeostasis model assessment-insulin resistance and negatively associated with HDL. Further studies are needed to understand the mechanism of low HDL and raised pigment epithelium-derived factor and to determine if they are causally related to the pathobiology of insulin resistance.

• Authors: S Pek, S Tavintharan, K Woon, J Niyati, S C Lim, C F Sum
• Journal: Diabetic medicine : a journal of the British Diabetic Association (Diabet Med) Vol. 30 Issue 9 Pg. 1067-74 (Sep 2013) ISSN: 1464-5491 [Electronic] England
• PMID: 23600479 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2013 The Authors. Diabetic Medicine © 2013 Diabetes UK.

Chemical References

• Eye Proteins
• Lipoproteins, HDL
• Nerve Growth Factors
• Serpins
• pigment epithelium-derived factor

Topics

• 3T3-L1 Cells
• Adipocytes, White (metabolism)
• Adolescent
• Adult
• Aged
• Animals
• Body Mass Index
• Cohort Studies
• Cross-Sectional Studies
• Diabetes Mellitus, Type 2 (blood, complications, metabolism)
• Eye Proteins (blood, metabolism)
• Female
• Follow-Up Studies
• Humans
• Insulin Resistance
• Lipoproteins, HDL (blood, metabolism)
• Male
• Mice
• Middle Aged
• Nerve Growth Factors (blood, metabolism)
• Overweight (complications)
• Prediabetic State (blood, complications, metabolism)
• Prospective Studies
• Serpins (blood, metabolism)
• Young Adult