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.
Highlights
Various metabolic pathways are involved in glucose homeostasis and in the development of insulin resistance
Patients were screened for any pre-existing diabetic condition; oral glucose tolerance test results were normal and excluded gestational diabetes
Adipose tissue plays a central role in the development of insulin resistance because it is insulin responsive and contributes directly, quantitatively less than skeletal muscle, to the whole-body glucose disposal [1] [4] [8] [27] [28]
Summary
Various metabolic pathways are involved in glucose homeostasis and in the development of insulin resistance. The PI3k/Akt pathway further stimulates the translocation of GLUT4 vesicles to the plasma membrane and allows the uptake of glucose into muscle and adipose cells [1]-[3]. The cellular mechanisms for decreased insulin sensitivity are multifactorial, involving both skeletal muscle and adipose tissue and remain to be completely elucidated [1] [4]. Human pregnancy is characterized by adipose tissue accretion in early gestation, followed by insulin resistance and facilitated lipolysis in late pregnancy [7]-[9]. The adipose tissue transcriptome demonstrates the recruitment of metabolic and immune molecular networks by 8 - 12 weeks of gestation, preceding any pregnancyrelated physiological changes associated with insulin resistance [9]
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