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


METHODS
In vivo and in vitro study.


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


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


METHODS
All subjects studied in the fasting state.


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


RESULTS
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.


CONCLUSIONS
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.
Aroda
Vanita
V
VA San Diego Healthcare System, San Diego, California; Department of Medicine, University, San Diego, La Jolla, California.
Ciaraldi
Theodore P
TP
VA San Diego Healthcare System, San Diego, California; Department of Medicine, University, San Diego, La Jolla, California.
Chang
Sang-Ah
SA
VA San Diego Healthcare System, San Diego, California; Department of Medicine, University, San Diego, La Jolla, California.
Dahan
Michael H
MH
Department of Reproductive Medicine, University of California, San Diego, California.
Chang
R Jeffrey
RJ
Department of Reproductive Medicine, University of California, San Diego, California.
Henry
Robert R
RR
VA San Diego Healthcare System, San Diego, California; Department of Medicine, University, San Diego, La Jolla, California. Electronic address: rrhenry@vapop.ucsd.edu.
D017667:Adipocytes / Q000378:metabolism* / Q000473:pathology; D052242:Adiponectin / Q000378:metabolism*; D000328:Adult; D001706:Biopsy; D015992:Body Mass Index; D016022:Case-Control Studies; D005260:Female; D005947:Glucose / Q000378:metabolism; D015309:Glucose Clamp Technique; D018149:Glucose Intolerance / Q000503:physiopathology*; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D009765:Obesity / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D011085:Polycystic Ovary Syndrome / Q000378:metabolism* / Q000473:pathology
D052242:Adiponectin; D007328:Insulin; D005947:Glucose
J Biol Chem. 2005 May 6;280(18):18073-80
15760892
Diabetes Care. 2003 Jul;26(7):2015-20
12832305
Metabolism. 2002 Mar;51(3):314-7
11887166
Biochem Biophys Res Commun. 2001 Feb 2;280(4):1120-9
11162643
Diabetes. 2001 May;50(5):1126-33
11334417
Diabetes. 2003 Mar;52(3):667-74
12606507
J Clin Endocrinol Metab. 2004 Jun;89(6):2548-56
15181022
Clin Chem. 2005 Feb;51(2):416-23
15590747
Diabetes. 2002 Oct;51(10):2968-74
12351435
Nature. 1970 Aug 15;227(5259):680-5
5432063
Eur J Endocrinol. 2005 Sep;153(3):409-17
16131604
Horm Metab Res. 2002 Nov-Dec;34(11-12):650-4
12660876
Am J Physiol Endocrinol Metab. 2006 Nov;291(5):E1100-5
16803857
J Biol Chem. 1964 Feb;239:375-80
14169133
Hum Reprod. 2003 Sep;18(9):1790-6
12923129
Obstet Gynecol Surv. 2006 Feb;61(2):125-35
16433936
J Clin Endocrinol Metab. 2003 Jun;88(6):2619-23
12788865
Diabetes. 2002 Sep;51(9):2734-41
12196466
J Clin Endocrinol Metab. 1998 Sep;83(9):3078-82
9745406
J Biol Chem. 2003 Mar 14;278(11):9073-85
12496257
Clin Endocrinol (Oxf). 2004 Dec;61(6):738-46
15579189
J Clin Endocrinol Metab. 2003 Dec;88(12):5624-31
14671144
J Soc Gynecol Investig. 2005 Feb;12(2):129-34
15695109
J Endocrinol Invest. 2004 Jun;27(6):528-34
15717649
J Clin Endocrinol Metab. 2004 Sep;89(9):4312-9
15356026
Best Pract Res Clin Obstet Gynaecol. 2004 Oct;18(5):803-12
15380148
Diabetes. 2004 Sep;53(9):2473-8
15331562
J Biol Chem. 2003 Oct 10;278(41):40352-63
12878598
Am J Physiol. 1979 Sep;237(3):E214-23
382871
Diabetes Care. 2003 Dec;26(12):3226-9
14633806
J Clin Endocrinol Metab. 2004 Aug;89(8):4053-61
15292348
J Biol Chem. 1995 Nov 10;270(45):26746-9
7592907
Diabetes. 1990 Feb;39(2):250-9
2227134
J Clin Invest. 1990 Feb;85(2):522-9
2105341
Lancet. 2002 Jul 6;360(9326):57-8
12114044
Diabetes. 1982 Nov;31(11):1016-22
6757010
Diabetes Care. 2004 Jan;27 Suppl 1:S5-S10
14693921
J Biol Chem. 2004 Mar 26;279(13):12152-62
14699128
J Clin Endocrinol Metab. 2001 May;86(5):1930-5
11344187
J Biol Chem. 2003 Dec 12;278(50):50810-7
14522956
Diabetes. 2006 Jul;55(7):1954-60
16804063
Nat Med. 2001 Aug;7(8):941-6
11479627
J Clin Endocrinol Metab. 1983 Aug;57(2):356-9
6223044
Biochem Biophys Res Commun. 1996 Apr 16;221(2):286-9
8619847