title: Role of IGFBP-3 in the regulation of β-cell mass during obesity: adipose tissue/β-cell cross talk.
abstract: 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 proliferation rate, the blockage of IGF-I receptor decreased it. Taken together, these data show that obesity induces specific changes in the expression profile of the adipose tissue depot surrounding the pancreas, leading to a decrease in IGFBP3 secretion. This decrease acts in a paracrine manner, stimulating the β-cell proliferation rate, probably through an IGF-I-dependent mechanism. This cross talk between the visceral-pancreatic adipose tissue and β-cells is a novel mechanism that participates in the control of β-cell plasticity.
authors: Diabetes and Obesity Laboratory, Institut d'Investigations Biomediques August Pi i Sunyer, Rosselló 149-153, E-08036 Barcelona, Spain.
authors: Nuria
authors: N
authors: Palau
authors: Sandra A
authors: SA
authors: Rebuffat
authors: Jordi
authors: J
authors: Altirriba
authors: Sandra
authors: S
authors: Piquer
authors: Felicia A
authors: FA
authors: Hanzu
authors: Ramon
authors: R
authors: Gomis
authors: Albert
authors: A
authors: Barbera
mesh_terms: D000273:Adipose Tissue / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D001483:Base Sequence; D002452:Cell Count; D002460:Cell Line; D049109:Cell Proliferation; D017077:Culture Media, Conditioned; D004032:Diet / Q000009:adverse effects; D004195:Disease Models, Animal; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000235:genetics / Q000502:physiology*; D050417:Insulin-Secreting Cells / Q000473:pathology* / Q000502:physiology*; D008297:Male; D009765:Obesity / Q000209:etiology / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020239:Receptor Cross-Talk / Q000502:physiology
chemical_list: D017077:Culture Media, Conditioned; D018972:Insulin-Like Growth Factor Binding Protein 3; D012333:RNA, Messenger