Identification of a Novel Function of Adipocyte Plasma Membrane-Associated Protein (APMAP) in Gestational Diabetes Mellitus by Proteomic Analysis of Omental Adipose Tissue

Gestational
diabetes mellitus (GDM) is considered as an early stage
of type 2 diabetes mellitus. In this study, we compared demographic
and clinical data between six GDM subjects and six normal glucose
tolerance (NGT; healthy controls) subjects and found that homeostasis
model of assessment for insulin resistance index (HOMA-IR) increased
in GDM. Many previous studies demonstrated that omental adipose tissue
dysfunction could induce insulin resistance. Thus, to investigate
the cause of insulin resistance in GDM, we used label-free proteomics
to identify differentially expressed proteins in omental adipose tissues
from GDM and NGT subjects (data are available via ProteomeXchange
with identifier PXD003095). A total of 3528 proteins were identified,
including 66 significantly changed proteins. Adipocyte plasma membrane-associated
protein (APMAP, a.k.a. C20orf3), one of the differentially expressed
proteins, was down-regulated in GDM omental adipose tissues. Furthermore,
mature 3T3-L1 adipocytes were used to simulate omental adipocytes.
The inhibition of APMAP expression by RNAi impaired insulin signaling
and activated NFκB signaling in these adipocytes. Our study
revealed that the down-regulation of APMAP in omental adipose tissue
may play an important role in insulin resistance in the pathophysiology
of GDM.