Insulin resistance in polycystic ovary syndrome: decreased expression of GLUT-4 glucose transporters in adipocytes

Abstract

We have found that women with polycystic ovary syndrome (PCOS) have decreased sensitivity and responsiveness to insulin. The present study was performed to determine whether this impaired insulin responsiveness was associated with diminished GLUT-4 glucose transporter content in adipocytes. Insulin-stimulated glucose transport and GLUT-4 abundance were measured in abdominal adipocytes from obese (n = 9) and lean (n = 7) PCOS as well as obese (n = 8) and lean (n = 8) control women matched for age and weight. No woman had impaired glucose tolerance. The maximal insulin-stimulated increment in adipocyte glucose transport was independently decreased by obesity and by PCOS. As expected, GLUT-4 content in adipocyte membranes was decreased in obesity (by 40%, P < or = 0.01). GLUT-4 content was also significantly decreased in PCOS (by 36%, P < or = 0.01), independent of obesity. There was a highly significant correlation (R = 0.66, P < = 0.001) between GLUT-4 content and insulin-stimulated glucose transport in adipocytes from individual women across the study population. We conclude that the diminished adipocyte insulin responsiveness in PCOS is associated with decreased GLUT-4 abundance. This represents a newly recognized phenotypic feature of the insulin resistance of PCOS. Moreover, in human adipocytes, GLUT-4 abundance is highly correlated with insulin responsiveness.

The adipose tissue metabolism: role of testosterone and dehydroepiandrosterone

“…27 Rosenbaum et al also demonstrated that the insulin resistance on the glucose transport is strictly associated with a decreased expression of GLUT-4 glucose transporters in adipocytes. 28 …”

Nutrition, insulin and polycystic ovary syndrome

“…First, resistance to the action of insulin affects peripheral glucose uptake and insulin-mediated suppression of lipolysis, but does not appear to extend to the hepatic actions of insulin (Peiris et al, 1989;Dunaif, 1993). This is borne out by the well recognized, inverse relationship of serum concentrations of insulin and sex hormone binding globulin (SHBG), which is presumed to be a reflection of the direct inhibitory action of insulin on SHBG synthesis by the liver (Plymate et al, 1988;Conway et al, 1990;Sharp et al, 1991;Hamilton-Fairley et al, 1995).…”

“…The differences in insulin sensitivity between PCOS and BMI-matched control groups are no longer significant if the distribution of body fat is taken into account (Robinson et al, 1992;Holte et al, 1994). Third -and this is not surprising, given the apparently tissue-selective nature of insulin resistance -there is little evidence for a primary abnormality in the insulin receptor in PCOS (Dunaif, 1993). While it is true that genetically determined defects in the insulin receptor can lead to the development of a PCOS-like syndrome, it must be conceded that women with these receptor disorders constitute only a very small proportion of those presenting with hyperandrogenism (Dunaif, 1993).…”

“…Third -and this is not surprising, given the apparently tissue-selective nature of insulin resistance -there is little evidence for a primary abnormality in the insulin receptor in PCOS (Dunaif, 1993). While it is true that genetically determined defects in the insulin receptor can lead to the development of a PCOS-like syndrome, it must be conceded that women with these receptor disorders constitute only a very small proportion of those presenting with hyperandrogenism (Dunaif, 1993). Data from studies of adipocytes derived from women with PCOS and controls suggest that there is a post-receptor abnormality in the insulin signalling pathway (Ciaraldi et al, 1992;Dunaif et al, 1992;Rosenbaum et al, 1993).…”

“…While it is true that genetically determined defects in the insulin receptor can lead to the development of a PCOS-like syndrome, it must be conceded that women with these receptor disorders constitute only a very small proportion of those presenting with hyperandrogenism (Dunaif, 1993). Data from studies of adipocytes derived from women with PCOS and controls suggest that there is a post-receptor abnormality in the insulin signalling pathway (Ciaraldi et al, 1992;Dunaif et al, 1992;Rosenbaum et al, 1993). In particular, there is evidence that up to 50% of patients with PCOS demonstrate constitutive abnormalities in receptor autophosphorylation, which is an integral part of the normal intracellular signalling function of the insulin receptor (Book et al, 1995).…”