Cellular insulin resistance in adipocytes from obese polycystic ovary syndrome subjects involves adenosine modulation of insulin sensitivity.
Cellular insulin resistance in polycystic ovary syndrome (PCOS) has been shown to involve a novel postbinding defect in insulin signal transduction. To find possible mechanisms for this defect, adipocytes were isolated from age- and weight-matched obese normal cycling (NC) and PCOS subjects. Insulin sensitivity for glucose transport stimulation was impaired in PCOS adipocytes (EC50 = 290 +/- 42 pmol/L) compared to that in NC cells (93 +/- 14; P < 0.005). The lipolytic responses to isoproterenol as well as maximal suppression by insulin were similar in NC and PCOS adipocytes. However, PCOS cells were less sensitive to the antilipolytic effect of insulin (EC50 = 115 +/- 33 pmol/L) compared to NC cells (42 +/- 8; P < 0.01). Treatment of adipocytes from NC subjects with the adenosine receptor agonist N6-phenylisopropyl adenosine had no effect on either insulin responsiveness or sensitivity for glucose transport stimulation. However, N6-phenylisopropyl adenosine treatment was able to normalize insulin sensitivity in PCOS cells (EC50 = 285 +/- 47 vs. 70 +/- 15 pmol/L, before and after treatment; P < 0.05). In conclusion, our results suggest that insulin resistance in PCOS, as accessed in the adipocyte, occurs at an early step in insulin signaling that is common for glucose transport and lipolysis. In addition, this insulin resistance involves an impairment of the system by which adenosine acts to modulate insulin signal transduction.
Ciaraldi
T P
TP
Department of Medicine, University of California-San Diego, La Jolla 92093, USA. tciaraldi@ucsd.edu
Morales
A J
AJ
Hickman
M G
MG
Odom-Ford
R
R
Olefsky
J M
JM
Yen
S S
SS
D000241:Adenosine / Q000494:pharmacology*; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000328:Adult; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology; D007333:Insulin Resistance; D007545:Isoproterenol / Q000494:pharmacology; D008066:Lipolysis; D007986:Luteinizing Hormone / Q000097:blood; D009765:Obesity / Q000209:etiology* / Q000378:metabolism; D011085:Polycystic Ovary Syndrome / Q000150:complications* / Q000378:metabolism; D013739:Testosterone / Q000097:blood
D000318:Adrenergic beta-Agonists; D007328:Insulin; D013739:Testosterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D005947:Glucose; D000241:Adenosine; D007545:Isoproterenol