Circulating and cellular adiponectin in polycystic ovary syndrome: relationship to glucose tolerance and insulin action
Received 12 October 2006; received in revised form 24 April 2007; accepted 25 April 2007. published online 14 August 2007.
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 μg/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 μg 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.
aVA San Diego Healthcare System, San Diego, California
bDepartment of Medicine, University, San Diego, La Jolla, California
cDepartment of Reproductive Medicine, University of California, San Diego, California
Reprint requests: Robert R. Henry, M.D., VA San Diego Healthcare System, mail code 111G, 3350 La Jolla Village Drive, San Diego, CA 92161 (FAX: 858-642-6242).
Present address of Dr. Sang-Ah Chang: Department of Internal Medicine, Catholic University of Korea, Seoul, Korea.
Present address of Dr. Michael H. Dahan: Department of Obstetrics and Gynecology, Stanford University, 300 Pasteur Dr., Stanford, CA 94305.
R.R.H. is a consultant, member of the advisory board, and has received a research grant from Takeda Pharmaceuticals North America.
Supported by the Department of Veterans Affairs, the VA San Diego Healthcare System, the American Diabetes Association (T.P.C., R.R.H.), American Diabetes Association Mentor-based Fellowship (R.R.H.), NIH ROI-DK-258291 (R.R.H.), National Institute of Child Health and Human Development/National Institutes of Health through cooperative agreement (U54 HD 12303-20) as part of the Specialized Cooperative Centers Program in Reproduction Research (R.J.C.), Takeda Pharmaceuticals North America (R.R.H.), and grant MO1 RR-00827 from the General Clinical Research Branch, Division of Research Resources, National Institutes of Health.
Presented at 64th Scientific Sessions of the American Diabetes Association, Orlando, Florida, June 4–8, 2004.
ABSTRACT