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Insulin resistance is associated with elevated serum pigment epithelium–derived factor (PEDF) levels in morbidly obese patients

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Abstract

Obesity is a significant risk factor for developing diabetes. Pigment epithelium–derived factor (PEDF) has been identified by experimental and clinical studies as both a causative and counter-regulatory factor in the metabolic syndrome. We set out to determine whether serum PEDF levels correlated with the degree of insulin resistance in morbidly obese patients. Sera from 53 patients who were evaluated prior to gastric bypass surgery were analyzed for PEDF levels using a commercial ELISA. None of the patients were on diabetes medications prior to enrollment. Baseline data included BMI, serum glucose and insulin, and homeostasis model assessment (HOMA) scores. Patients were stratified based on HOMA score and glucose levels into three groups: insulin sensitive (IS): HOMA <2 and glucose <126; insulin resistant (IR): HOMA >2 and glucose ≤126; and diabetes mellitus (DM): HOMA >2 and glucose >126. Pre- and post-gastric bypass sera from 12 patients were obtained for serial assessment of metabolic parameters and PEDF levels. PEDF secretion was assessed in primary human hepatocytes, HCC cells, and cultured adipocytes in the absence and presence of high glucose media. No significant differences in age, gender, and BMI were found among the three groups. PEDF levels were similar between IR patients and the other groups, but were significantly higher in DM compared to IS patients (p = 0.01). Serum PEDF in individual patients declined significantly after gastric bypass (p = 0.006). High glucose media led to significantly higher PEDF release by human hepatocytes in vitro (p = 0.016). These data demonstrate that serum PEDF concentrations better relate to insulin resistance than to adiposity and suggest that PEDF expression is closely linked to the development of insulin resistance.

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Abbreviations

HOMA:

Homeostasis model assessment

PEDF:

Pigment epithelium–derived factor

TG:

Triglyceride

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Acknoweledgments

V.T.S. VA Merit Review Award and U24 DK59635; C.C. VA Merit Review Award, CDA-2 Award.

Conflict of interest

The authors declare that they have no competing financial interests.

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Authors and Affiliations

  1. Veteran’s Affairs Medical Center, West Haven, CT, USA

    Arijeet K. Gattu, Chuhan Chung & Varman Samuel

  2. Yale University School of Medicine, New Haven, CT, USA

    Arijeet K. Gattu, Andreas L. Birkenfeld, Francois Jornayvaz, James Dziura, Fangyong Li, Chuhan Chung & Varman Samuel

  3. Northshore Research Institute, Evanston, IL, USA

    Susan E. Crawford

  4. Weis Center for Research, Geisinger Clinic, Danville, PA, USA

    Xin Chu, Christopher D. Still & Glenn S. Gerhard

  5. Section of Digestive Diseases, GI Research Bldg 4, West Haven, CT, 06516, USA

    Chuhan Chung

  6. Section of Endocrinology, West Haven VAMC, MC 151, West Haven, CT, 06516, USA

    Varman Samuel

Authors
  1. Arijeet K. Gattu
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  2. Andreas L. Birkenfeld
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  3. Francois Jornayvaz
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  4. James Dziura
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  5. Fangyong Li
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  6. Susan E. Crawford
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  7. Xin Chu
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  8. Christopher D. Still
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  9. Glenn S. Gerhard
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  10. Chuhan Chung
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  11. Varman Samuel
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Corresponding authors

Correspondence to Chuhan Chung or Varman Samuel.

Additional information

Communicated by Renato Lauro.

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Gattu, A.K., Birkenfeld, A.L., Jornayvaz, F. et al. Insulin resistance is associated with elevated serum pigment epithelium–derived factor (PEDF) levels in morbidly obese patients. Acta Diabetol 49 (Suppl 1), 161–169 (2012). https://doi.org/10.1007/s00592-012-0397-y

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  • DOI: https://doi.org/10.1007/s00592-012-0397-y

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