TITLE:
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
AUTHORS:
Arnold M. Mahesan, Dotun Ogunyemi, Eric Kim, Anthea B. M. Paul, Y.-D. Ida Chen
KEYWORDS:
DEG, Insulin Resistance, Insulin Sensitivity, Insulin Signaling Pathway, Adipose Tissue in Pregnancy, Carbohydrate Metabolism, Diabetic Pathways
JOURNAL NAME:
Journal of Diabetes Mellitus,
Vol.6 No.1,
February
29,
2016
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.