Insulin-like growth factor II signaling through the insulin-like growth factor II/mannose-6-phosphate receptor promotes exocytosis in insulin-secreting cells.
The insulin-like growth factor II (IGF-II)/mannose-6-phosphate (M-6-P) receptor is known to participate in endocytosis as well as sorting of lysosomal enzymes and is involved in membrane trafficking through rapid cycling between cytosolic membrane compartments and the plasma membrane. Here we demonstrate that IGF-II, acting through the IGF-II/M-6-P receptor, promotes exocytosis of insulin in the pancreatic beta cell. The effect of IGF-II was evoked at nonstimulatory concentrations of glucose, was mediated by a pertussis toxin sensitive GTP-binding protein, was dependent on protein kinase C-induced phosphorylation, and was independent of changes in cytoplasmic free Ca2+ concentration. Since the applied concentration of IGF-II is within the range normally found free in circulation in humans, this novel signaling pathway for the IGF-II/M-6-P receptor is likely to be involved in modulation of insulin exocytosis under physiological conditions.
Zhang
Q
Q
Department of Molecular Medicine, The Rolf Luft Center for Diabetes Research, Karolinska Institute, S-171 76 Stockholm, Sweden.
Tally
M
M
Larsson
O
O
Kennedy
R T
RT
Huang
L
L
Hall
K
K
Berggren
P O
PO
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D005089:Exocytosis / Q000187:drug effects*; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007335:Insulin-Like Growth Factor II / Q000378:metabolism / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D007700:Kinetics; D051379:Mice; D008820:Mice, Obese; D011493:Protein Kinase C / Q000378:metabolism; D017527:Receptor, IGF Type 2 / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014044:Tolbutamide / Q000494:pharmacology
D007328:Insulin; D017527:Receptor, IGF Type 2; D007335:Insulin-Like Growth Factor II; D000255:Adenosine Triphosphate; D014044:Tolbutamide; D011493:Protein Kinase C; D005947:Glucose; D013755:Tetradecanoylphorbol Acetate