Adipocyte expression of glucose transporter 1 and 4 in PCOS: Relationship to insulin‐mediated and non–insulin‐mediated whole‐body glucose uptake

Summary Background Polycystic ovary syndrome (PCOS) is a highly prevalent endocrine‐metabolic disorder associated with insulin resistance (IR). In IR states, non–insulin‐mediated glucose uptake (NIMGU) may increase to compensate for declining insulin‐mediated glucose uptake (IMGU), although this does not appear to be the case in PCOS. The underlying molecular mechanisms for this deficiency remain unclear. Objectives To compare adipocyte glucose transporter 1 and 4 (GLUT‐1 and GLUT‐4) gene expression in PCOS women and matched controls, and to determine whether changes in GLUT‐1 and GLUT‐4 are associated with concomitant alterations in whole‐body glucose uptake. Research design and methods In this prospective cross‐sectional study, 23 women with PCOS (by NIH 1990 criteria) and 23 matched controls were studied for subcutaneous abdominal adipocyte GLUT‐1 and GLUT‐4 mRNA expression (by real‐time PCR), and basal whole‐body IR (by HOMA‐IR) and insulin secretion (by HOMA‐β%). A subset of six PCOS women and six matched controls also underwent a mFSIVGTT to determine dynamic state glucose uptake (by insulin sensitivity index [Si] and glucose effectiveness [Sg]) and insulin secretion (by the acute insulin response to glucose [AIRg] and the disposition index [Di]). Results For similar adiposity (BMI and waist‐hip ratio), PCOS women tended to have higher HOMA‐IR and lower Di and Si, and higher HOMA‐β% and lower GLUT‐4 than controls, while GLUT‐1 was similar. GLUT‐1 was positively associated with Sg (reflecting NIMGU) and GLUT‐4 positively with Si (reflecting IMGU). GLUT‐4 was associated negatively with HOMA‐IR and HOMA‐β% and positively with Di for the entire cohort but not with AIRg. Both GLUT‐1 and GLU‐4 were negatively associated with BMI, but not with each other. Conclusion Our results suggest that IR secondary to a lower IMGU and enhanced insulin secretion in PCOS is in part attributable to a reduction in adipocyte GLUT‐4 expression that is not accompanied by a compensatory increase in GLUT‐1 expression.