Circulating and cellular adiponectin in polycystic ovary syndrome: relationship to glucose tolerance and insulin action

Abstract

Objective: To evaluate serum adiponectin levels and organization into multimers in women with polycystic ovary syndrome (PCOS) and assess relationships between adiponectin, glucose tolerance, and insulin resistance.

Design: In vivo and in vitro study.

Setting: Outpatient clinic at university and Veterans hospitals in the United States and university laboratory.

Patient(s): Thirty-one obese women with PCOS and six age- and body mass index (BMI)-matched normal cycling control subjects.

Intervention(s): All subjects studied in the fasting state.

Main outcome measure(s): A 75-g oral glucose tolerance test (OGTT), hyperinsulinemic/euglycemic clamp, circulating adiponectin levels, adipocyte adiponectin content, and organization of adiponectin into multimeric forms.

Result(s): Whole body insulin action (glucose disposal rate, 5.61 +/- 2.90 vs. 8.79 +/- 0.81 mg/kg/min, PCOS and control) and adiponectin levels (9.5 +/- 0.7 7 vs. 17.4 +/- 1 microg/mL, PCOS vs. control) were significantly reduced in the subjects with PCOS. There were significant correlations between glucose tolerance, insulin action, and circulating adiponectin levels in all subjects. The content of adiponectin protein was reduced in subcutaneous adipocytes from subjects with PCOS (252 +/- 31 vs. 388 +/- 58 arbitrary units/10 microg protein). Subjects with PCOS had less of their circulating adiponectin organized into high molecular weight (HMW) multimeric complexes. Glucose-intolerant subjects with PCOS also had less intracellular HMW adiponectin.

Conclusion(s): Both circulating adiponectin levels and the portion present as the most active HMW form are reduced in PCOS, with differences related to the degree of glucose intolerance and insulin resistance.

FIGURE 1

Whole body insulin action (insulin-stimulated glucose disposal rate) (A) and circulating adiponectin levels (B) in normal cycling control subjects (control [Cont], n = 6) and subjects with polycystic ovary syndrome (PCOS) categorized as normal glucose tolerant (NGT, n = 13), and impaired glucose response (IGR, n = 18). All values reported as average ±SEM. *P<.02 vs. control.

FIGURE 2

Distribution of adiponectin between multimers in the serum of control, normal glucose tolerant– polycystic ovary syndrome (NGT-PCOS) and impaired glucose response (IGR)-PCOS subjects. Equal amounts (2 μL) of serum loaded for each individual. (A) Representative Western blots of 2%−8% tris-acetate gels run under nonreducing conditions. (B) Quantitation of blots. Results are expressed as percent of the total densitometric signal for each individual, within each lane. Results are average ±SEM, n = 6 for control, 10 for NGT, 16 for IGR. *P<.05 vs. control (Cont). HMW = high molecular weight; MMW = medium molecular weight; LMW = low molecular weight.

FIGURE 3

Distribution of adiponectin between multimers in adipocytes of control, normal glucose tolerant– polycystic ovary syndrome (PCOS) and impaired glucose response-PCOS subjects. (A) Representative Western blots. Equal amounts of cell protein (10 mg) loaded for each individual. (B) Quantitation of blots. Results are expressed as percent of the total densitometric signal in each lane for each individual. Results are average ±SEM, n = 6 for control, 6 for NGT, and 16 for IGR. *P<.05 vs. control (Cont). HMW = high molecular weight; MMW = medium molecular weight; LMW = low molecular weight.