Upregulation of a2m signalling receptor by insulin in macrophages

In 1984 this laboratory showed that the treatment of adipocytes and fibrob lasts with insulin enhanced the binding of 125I-a2M-methylamine by about 2-3 fold and its slowed receptor-mediated degradation. We have recently reported the presence of a novel ojM signaling receptor on macrophage cell surface. This receptor is distinct from LRP/cMR in several aspects including the presence of very high affinity binding sites for the cognate ligands (Kd pM), its lack of inhibition by RAP and Ni, and its pertussis toxin insenskivity. To understand the possible mechanism of insulin-induced enhanced binding of 125I-02Mmethylamine, we have studied the binding of 125I-a2M-methylamine to tMSR, its inhibition by RAP, quantified rnRNA levels of LRP/a2MR/a2MR, signal ing events in macrophages treated with insulin. Insulin treatment increased the binding of ajM-methylamine to both high ( 2500 sites) and low affinity binding sites {115000 sites) by about 2-3 fold but RAP inhibited the binding only to low affinity binding sites. Insulin-induced mRNA levels of this receptor were drastically reduced by prior treatment with actinomycin D. Insulin treatment caused an 2-4 fold increase in intracellular inositol (1,4,5-) triphsophate and calcium levels which were abolished or drastically reduced by prior treatment with actinomycin D, cycloheximide, genestein, staurosporin and antibody against the insulin receptor.

Duke Scholars

Author Mario Gonzalez-Gronow Pathology

Author Salvatore Vincent Pizzo Pathology

Author Uma Kant Misra Pathology