Glucose increases both the plasma membrane number and phosphorylation of insulin-like growth factor II/mannose 6-phosphate receptors.
We have investigated the effect of glucose on insulin-like growth factor II (IGF-II) binding to, and intracellular phosphorylation of, the IGF-II/mannose 6-phosphate (M6P) receptor in the insulin-secreting cell line RINm5F. Glucose, at a concentration of 3 mM, significantly increased binding of IGF-II to the cells. A further increase of the binding was observed at a glucose concentration of 10 mM. Scatchard analysis showed that the increased binding was caused by an increased number of the receptors rather than changes in affinity. This effect of glucose was also demonstrated in another insulin-secreting cell line HIT as well as in the human erythroleukemia cell line K562. Affinity cross-linking of the RINm5F cells, using 125I-IGF-II, revealed increased binding to the IGF-II/M6P receptor induced by glucose. The effect of glucose on IGF-II binding was mimicked by fructose (10 mM), but not by 3-O-methylglucose (10 mM), and was abolished by the protein kinase C (PKC) inhibitor calphostin C, or down-regulation of PKC, but not by the protein phosphatase inhibitor, okadaic acid. Glucose dose dependently stimulated phosphorylation of the IGF-II/M6P receptor, an effect that was inhibited by down-regulation of PKC activity. This study suggests that the distribution of the IGF-II/M6P receptor in insulin-secreting cells can be regulated by glucose-induced phosphorylation, a mechanism mediated by PKC.
Zhang
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Department of Molecular Medicine, Endocrine and Diabetes Unit, the Rolf Luft Center for Diabetes Research, Karolinska Institute, S-171 76, Stockholm, Sweden.
Berggren
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PO
Tally
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D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D007457:Iodine Radioisotopes; D010766:Phosphorylation; D011485:Protein Binding; D051381:Rats; D017527:Receptor, IGF Type 2 / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D007457:Iodine Radioisotopes; D017527:Receptor, IGF Type 2; D007335:Insulin-Like Growth Factor II; D005947:Glucose