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

Abstract

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 wholebody 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. K E Y W O R D Sadipocyte GLUT-1, GLUT-4, insulin resistance, polycystic ovary syndrome | 543 EZEH Et al.

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“…In another paper, the same research group also compared GLUT1 and GLUT4 mRNA levels in adipocytes of PCOS women and matched controls. Their results suggest that IR secondary to lower insulinmediated glucose uptake and enhanced insulin secretion in PCOS is partly attributable to a reduction in adipocyte GLUT4 expression that is not accompanied by a compensatory increase in GLUT1 expression [30].…”

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“…The decrease of glucose uptake and utilization by skeletal muscle and adipocytes caused by the decrease of GLUT4 expression or activity is an important molecular basis of IR. A prospective crosssectional study showed that IR secondary to PCOS insulinmediated decreased glucose uptake and increased insulin secretion was partly due to decreased GLUT4 expression in adipocytes without a compensatory increase in GLUT1 expression (34). The analysis of signaling components of the IRS/PI3K/AKT pathway showed that the expression of GLUT4 was significantly decreased in PCOS patients and the IR control group (35).…”

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“…This explains why IR is often associated with compensatory hyperinsulinemia [ 92 , 94 , 95 ]. Many studies have shown that the decrease of glucose transporter type 4 (GLUT-4) expression is one of the mechanisms underlying IR and PCOS [ 96 – 98 ]. Feng et al found that insulin resistance reduced the expression of sex hormone-binding protein (SHBG) in human villous trophoblast cells, thereby inhibiting the expression of GLUT-4 and phosphatidylinositol 3-kinase (PI3K) p85α mRNA.…”