Role of IGFBP-3 in the Regulation of β-Cell Mass during Obesity: Adipose Tissue/β-Cell Cross Talk

In obesity an increase in β-cell mass occurs to cope with the rise in insulin demand. This β-cell plasticity is essential to avoid the onset of hyperglycemia, although the molecular mechanisms that regulate this process remain unclear. This study analyzed the role of adipose tissue in the control of β-cell replication. Using a diet-induced model of obesity, we obtained conditioned media from three different white adipose tissue depots. Only in the adipose tissue depot surrounding the pancreas did the diet induce changes that led to an increase in INS1E cells and the islet replication rate. To identify the factors responsible for this proliferative effect, adipose tissue gene expression analysis was conducted by microarrays and quantitative RT-PCR. Of all the differentially expressed proteins, only the secreted ones were studied. IGF binding protein 3 (Igfbp3) was identified as the candidate for this effect. Furthermore, in the conditioned media, although the blockage of IGFBP3 led to an increase in the pr...