Over-expression of NYGGF4 inhibits glucose transport in 3T3-L1 adipocytes via attenuated phosphorylation of IRS-1 and Akt

Abstract

Aim: NYGGF4 is a novel gene that is abundantly expressed in the adipose tissue of obese patients. The purpose of this study was to investigate the effects of NYGGF4 on basal and insulin-stimulated glucose uptake in mature 3T3-L1 adipocytes and to understand the underlying mechanisms. Methods: 3T3-L1 preadipocytes transfected with either an empty expression vector (pcDNA3.1Myc/His B) or an NYGGF4 expression vector were differentiated into mature adipocytes. Glucose uptake was determined by measuring 2-deoxy-D-[3 H]glucose uptake into the adipocytes. Immunoblotting was performed to detect the translocation of insulin-sensitive glucose transporter 4 (GLUT4). Immunoblotting also was used to measure the phosphorylation and total protein contents of insulin signaling proteins such as the insulin receptor (IR), insulin receptor substrate (IRS)-1, Akt, ERK1/2, p38, and JNK. Results: NYGGF4 over-expression in 3T3-L1 adipocytes reduced insulin-stimulated glucose uptake and impaired insulinstimulated GLUT4 translocation. It also diminished insulin-stimulated tyrosine phosphorylation of IRS-1 and serine phosphorylation of Akt without affecting the phosphorylation of IR, ERK1/2, p38, and JNK. Conclusion: NYGGF4 regulates the functions of IRS-1 and Akt, decreases GLUT4 translocation and reduces glucose uptake in response to insulin. These observations highlight the potential role of NYGGF4 in glucose homeostasis and possibly in the pathogenesis of obesity.

Cardiac-Specific PID1 Overexpression Enhances Pressure Overload-Induced Cardiac Hypertrophy in Mice

“…PID1 is highly expressed in the heart, suggesting a possible function for PID1 in cardiac disease. Previously studies indicated that PID1 acts directly on the IRS1/PI3K/AKT insulin pathway to reduce glucose uptake and transport and impairs mitochondrial function in adipose tissue [9]. Whether energy metabolism abnormality or mitochondrial dysfunction is thought to be tightly associated with the development of cardiac hypertrophy [10].…”

Porcine phosphotyrosine interaction domain containing 1 modulates 3T3-L1 preadipocyte proliferation and differentiation

“…Until now, research topics focus on the PID1 gene cloning, the relationship between PID1 and insulin resistance, and the underlying mechanism and signal pathways of its role in insulin resistance (Zhang et al 2009;Zhao et al 2010a,b;Man et al 2011;Wu et al 2011;Chen et al 2012).…”

Inhibition of PID1/NYGGF4/PCLI1 gene expression highlights its role in the early events of the cell cycle in NIH3T3 fibroblasts

“…Extensive screening efforts also validated the interaction of PCLI1 with the cytosolic domain of LRP1, highlighting also the reduced expression of the gene in early Alzheimer's disease 3 . A series of studies, mainly based on the stable overexpression of PCLI1, led to the characterization of the function of the gene in signal transduction and insulin resistance [4][5][6] . Indeed, ectopic expression of its cDNA in 3T3-L1 pre-adipocytes or in skeletal myotubes reduced insulin-stimulated Tyr phosphorylation of IRS-1 and Ser phosphorylation of AKT, resulting in the inhibition of insulin-stimulated glucose uptake through attenuation of the PI3K signaling pathway.…”