Pancreatic β-cell dysfunction in polycystic ovary syndrome: Role of hyperglycemia-induced nuclear factor-κB activation and systemic inflammation

Steven K. Malin, John P. Kirwan, Chang Ling Sia, Frank González

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

In polycystic ovary syndrome (PCOS), oxidative stress is implicated in the development of b-cell dysfunction. However, the role of mononuclear cell (MNC)-derived inflammation in this process is unclear. We determined the relationship between β-cell function and MNC-derived nuclear factor-κB (NF-κB) activation and tumor necrosis factor-α (TNF-α) secretion in response to a 2-h 75-g oral glucose tolerance test (OGTT) in normoglycemic women with PCOS (15 lean, 15 obese) and controls (16 lean, 14 obese). First- and second-phase b-cell function was calculated as glucose-stimulated insulin secretion (insulin/glucose area under the curve for 0–30 and 60–120 min, respectively) × insulin sensitivity (Matsuda Index derived from the OGTT). Glucose-stimulated NF-κB activation and TNF-α secretion from MNC, and fasting plasma thiobarbituric acid-reactive substances (TBARS) and high-sensitivity C-reactive protein (hs-CRP) were also assessed. In obese women with PCOS, first- and second-phase β-cell function was lower compared with lean and obese controls. Compared with lean controls, women with PCOS had greater change from baseline in NF-κB activation and TNF-α secretion, and higher plasma TBARS. β-Cell function was inversely related to NF-kB activation (1st and 2nd) and TNF-α secretion (1st), and plasma TBARS and hs-CRP (1st and 2nd). First- and second-phase -cell function also remained independently linked to NF-κB activation after adjustment for body fat percentage and TBARS. In conclusion, β-cell dysfunction in PCOS is linked to hyperglycemia-induced NF-κB activation from MNC and systemic inflammation. These data suggest that in PCOS, inflammation may play a role in impairing insulin secretion before the development of overt hyperglycemia.

Original languageEnglish (US)
Pages (from-to)E770-E777
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume308
Issue number9
DOIs
StatePublished - Jan 1 2015

Keywords

  • Androgens
  • Glucose intolerance
  • Insulin resistance
  • Insulin secretion
  • Insulin sensitivity
  • Mononuclear cells
  • Obesity

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Endocrinology, Diabetes and Metabolism

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