Insulin Resistance in Pregnancy Is Correlated with Decreased Insulin Receptor Gene Expression in Omental Adipose: Insulin Sensitivity and Adipose Tissue Gene Expression in Normal Pregnancy

Abstract

Aims: To determine correlations of insulin sensitivity to gene expression in omental and subcutaneous adipose tissue of non-obese, non-diabetic pregnant women. Methods: Microarray gene profiling was performed on subcutaneous and omental adipose tissue from 14 patients and obtained while fasting during non-laboring Cesarean section, using Illumina HumanHT-12 V4 Expression BeadChips. Findings were validated by real-time PCR. Matusda-Insulin sensitivity index (IS) and homeostasis model assessment of insulin resistance (HOMA-IR) were calculated from glucose and insulin levels obtained from a frequently sampled oral glucose tolerance test, and correlated with gene expression. Results: Of genes differentially expressed in omental vs. subcutaneous adipose, in omentum 12 genes were expressed toward insulin resistance, whereas only 5 genes were expressed toward insulin sensitivity. In particular, expression of the insulin receptor gene (INSR), which initiates the insulin signaling cascade, is strongly positively correlated with IS and negatively with HOMA-IR in omental tissue (r = 0.84). Conclusion: Differential gene expression in omentum relative to subcutaneous adipose showed a pro-insulin resistance profile in omentum. A clinical importance of omental adipose is observed here, as downregulation of insulin receptor in omentum is correlated with increased systemic insulin resistance.