Attenuation of insulin secretion by insulin-like growth factor binding protein-1 in pancreatic β-cells

IGFBP-1 is involved in glucohomeostasis, but the direct action of IGFBP-1 on the β-cell remains unclear. Incubation of dispersed mouse β-cells with IGFBP-1 for 30 min inhibited insulin secretion stimulated by glucose, glucagon-like peptide 1 (GLP-1) or tolbutamide without changes in basal release of insulin and in cytosolic free Ca2+ concentration ([Ca2+]i) and NAD(P)H evoked by glucose. In contrast, IGFBP-1 augmented glucose-stimulated insulin secretion in intact islets, associated with a reduced somatostatin secretion. These results suggest a suppressive action of IGFBP-1 on insulin secretion in isolated β-cells through a mechanism distal to energy generating steps and not involving regulation of [Ca2+]i. In contrast, IGFBP-1 amplifies glucose-stimulated insulin secretion in intact islets, possibly by suppressing somatostatin secretion. These direct modulatory influences of IGFBP-1 on insulin secretion may imply an important regulatory role of IGFBP-1 in vivo and in the pathogenesis of type 2 diabetes, in which loss of insulin release is an early pathogenetic event.