Attenuation of insulin secretion by insulin-like growth factor binding protein-1 in pancreatic beta-cells.
IGFBP-1 is involved in glucohomeostasis, but the direct action of IGFBP-1 on the beta-cell remains unclear. Incubation of dispersed mouse beta-cells with IGFBP-1 for 30min 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 Ca(2+) concentration ([Ca(2+)](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 beta-cells through a mechanism distal to energy generating steps and not involving regulation of [Ca(2+)](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.
Zhang
Fan
F
Research Center, Karolinska Institutet, South General Hospital, SE-11883, Stockholm, Sweden.
Sjöholm
Åke
Å
Research Center, Karolinska Institutet, South General Hospital, SE-11883, Stockholm, Sweden.
Zhang
Qimin
Q
Research Center, Karolinska Institutet, South General Hospital, SE-11883, Stockholm, Sweden. Electronic address: Qimin.Zhang@sos.ki.se.
D000818:Animals; D002118:Calcium / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D005089:Exocytosis; D052216:Glucagon-Like Peptide 1 / Q000737:chemistry; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000502:physiology*; D050417:Insulin-Secreting Cells / Q000378:metabolism; D051379:Mice; D008820:Mice, Obese; D008954:Models, Biological; D009249:NADP / Q000378:metabolism; D013004:Somatostatin / Q000378:metabolism
D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D013004:Somatostatin; D009249:NADP; D052216:Glucagon-Like Peptide 1; D005947:Glucose; D002118:Calcium