INSR and gestational diabetes: In addition, defective insulin signaling characterized by a significant increase in insulin receptor (IR) substrate (IRS)-1 protein expression with a concurrent decrease in IRS-2, phosphatidyl-inositol-3-kinase (PI3-K) p85a and glucose transporter (GLUT)- 4 protein expression has been demonstrated in GDM placentas, compared with normal controls [4].