Effects of monensin on insulin processing in adipocytes. Evidence that the internalized insulin-receptor complex has some physiological activities.

Ueda, Mirthes; Robinson, F W; Smith, M M; Kôno, Tetsuro

doi:10.1016/s0021-9258(18)89213-4

Cited by 41 publications

(5 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In contrast, insulin did not significantly stimulate MeAIB uptake in the PG19 melanoma cells.These results indicate that insulin does not stimulate system A amino acid transport in the melanoma cells, contrary to our previous conclusion(Coppock et al, 1980). removal of insulin from the medium(Ueda et al, 1985). This suggests that intracellular insulin-receptor complexes, which accumulate in the presence of monensin, retain residual ca-…”

contrasting

confidence: 94%

“…A number of studies have suggested a possible role for internalized insulin and/or insulin receptors in insulin action Podlecki et al, 1987;Ueda et al, 1985;Draznin & Trowbridge, 1982). Treatment of adipocytes with insulin plus monensin leads to a persistent partial activation of glucose transport and cAMP phosphodiesterase activity after pacity to stimulate glucose transport and phosphodiesterase activities.…”

Section: Discussionmentioning

confidence: 99%

“…Although the insulin receptors on the insulin-resistant PG19 melanoma cells appeared to be structurally normal, the possibility remained that receptor internalization and processing by the PG 19 cells may be abnormal. There is some indirect evidence that internalization of insulin receptors may be required to mediate certain biological effects of insulin Ueda et al, 1985). Therefore, internalization studies were performed to compare the fates of photolabeled insulin receptors on the PG19 and 100A cells.…”

Section: Comparison Of Insulinmentioning

confidence: 99%

See 2 more Smart Citations

Insulin receptor internalization defect in an insulin-resistant mouse melanoma cell line

Androlewicz¹,

Brandenburg²,

Straus³

1989

Biochemistry

View full text Add to dashboard Cite

Previous studies from this laboratory demonstrated that the PG19 mouse melanoma cell line does not exhibit a biological response to insulin, whereas melanoma x mouse embryo fibroblast hybrids do respond to insulin. To investigate the molecular basis of the insulin resistance of the PG19 melanoma cells, insulin receptors from the insulin-resistant melanoma cells and insulin-sensitive fibroblast x melanoma hybrid cells were analyzed by the technique of photoaffinity labeling using the photoprobe 125I-NAPA-DP-insulin. Photolabeled insulin receptors from the two cell types have identical molecular weights as determined by SDS gel electrophoresis under reducing and nonreducing conditions, indicating that the receptors on the two cell lines are structurally similar. Insulin receptor internalization studies revealed that the hybrid cells internalize receptors to a high degree at 37 degrees C, whereas the melanoma cells internalize receptors to a very low degree or not at all. The correlation between ability to internalize insulin receptors and sensitivity to insulin action in this system suggests that uptake of the insulin-receptor complex may be required for insulin action in these cells. Insulin receptors from the two cell lines autophosphorylate in a similar insulin-dependent manner both in vitro and in intact cells, indicating that insulin receptors on the melanoma and hybrid cells have functional tyrosine protein kinase activity. Therefore, the block in insulin action in the PG19 melanoma cells appears to reside at a step beyond insulin-stimulated receptor autophosphorylation.

show abstract

contrasting

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Section: Comparison Of Insulinmentioning

confidence: 99%

See 1 more Smart Citation

Insulin receptor internalization defect in an insulin-resistant mouse melanoma cell line

Androlewicz¹,

Brandenburg²,

Straus³

1989

Biochemistry

View full text Add to dashboard Cite

show abstract

“…A431 cells were treated with tunicamycin or monensin, drugs which inhibit different steps in glycosylation of proteins and have proven to be valuable tools for investigating the function of carboydrate chains (Ueda et al, 1985;King, 1984;Pryor & Buse, 1984;Doss et al, 1985). The effect of these treatments was evaluated on fiadrenergic ligand binding, agonist and antagonist, on expression of receptors and on amount of cyclic AMP accumulation induced by the agonist.…”

Section: Introductionmentioning

confidence: 99%

The β2-adrenergic receptors of human epidermoid carcinoma cells bear two different types of oligosaccharides which influence expression on the cell surface

Cervantes‐Olivier

Delavier-Klutchko

Durieu-Trautmann

et al. 1988

Biochemical Journal

View full text Add to dashboard Cite

The beta 2-adrenergic receptors of the human epidermoid carcinoma A431 cells reside on two polypeptide chains revealed by photoaffinity labelling with [125I]iodocyanopindolol-diazirine. These proteins correspond to two distinct populations of N-asparagine-linked glycoproteins: the 55-52 kDa molecules are associated with complex carbohydrate chain(s), the 65-63 kDa component with polymannosidic carbohydrate chain(s). Both types of receptors are present in preconfluent cells, but only the polymannosidic type is found in the postconfluent cells. Moreover, complex chains appear to be associated with the receptors with the highest affinity for (-)-isoproterenol and polymannosidic chains with the receptors with the lowest affinity for this agonist. the carbohydrate moiety of the beta-adrenergic receptor is involved in the expression and function of the beta 2-adrenergic receptors at the surface of the A431 cells, since tunicamycin and monensin, complete and partial inhibitors of glycosylation respectively, diminish the number of binding sites at the cell surface and increase the total number of sites in the cell. In these conditions a diminution of cyclic AMP accumulation is also observed.

show abstract

“…One important function of the internalization of insulin-receptor complexes is believed to be mediation of the insulin-induced receptor loss (down-regulation) that has been extensively demonstrated in various cell types, including adipocytes (15,18,24,29). Other potential functions of the internalization process may include the termination of insulin action by removing the hormone from the cell surface and transporting it to intracellular degradation sites and/or mediating the intracellular effects of the hormone (5,34,40). Thus, characterization of the internalization of insulinreceptor complexes is of importance in further understanding its role in the physiologic regulation of insulin receptors and insulin action.…”

mentioning

confidence: 99%

Chymotrypsin substrate analogues inhibit endocytosis of insulin and insulin receptors in adipocytes.

Jochen¹,

Berhanu²

1986

The Journal of Cell Biology

View full text Add to dashboard Cite

Abstract.To explore the possible role of proteolytic step(s) in receptor-mediated endocytosis of insulin, the effects of inhibitors of various classes of proteases on the internalization process were studied in isolated rat adipocytes. Intracellular accumulation of receptorbound 125I-insulin at 37°C was quantitated after rapidly dissociating surface-bound insulin with an acidic buffer (pH 3.0). Of the 23 protease inhibitors tested, only chymotrypsin substrate analogues inhibited insulin internalization. Internalization was decreased 62-90% by five different chymotrypsin substrate analogues: N-acetyl-Tyr ethyl ester, N-acetyl-Phe ethyl ester, N-acetyl-Trp ethyl ester, benzoyl-Tyr ethyl ester, and benzoyl-Tyr amide. The effect of the substrate analogues in inhibiting insulin internalization was dosedependent, reversible, and required the full structural complement of a chymotrypsin substrate analogue. Cell surface receptor number was unaltered at 12°C. However, concomitant with their inhibition of insulin internalization at 37°C, the chymotrypsin substrate analogues caused a marked increase (160-380%) in surface-bound insulin, indicating trapping of insulin-receptor complexes on the cell surface. Additionally, 1 mM N-acetyl-Tyr ethyl ester decreased overall insulin degradation by 15-20% and also prevented the chloroquine-mediated increase in intracellular insulin, further indicating that surface-bound insulin was prevented from reaching intracellular chloroquinesensitive degradation sites. The internalization of insulin receptors that were photoaffinity labeled on the cell surface with B2(2-nitro-4-azidophenylacetyl)-desPheBt-insulin was also inhibited 70-90% by the five chymotrypsin substrate analogues, as determined by the effects of the analogues on the accumulation of trypsin-insensitive (intracellular) 440-kD intact labeled receptors. In summary, these results show that chymotrypsin substrate analogues efficiently inhibit the internalization of insulin and insulin receptors in adipocytes and implicate a possible role for endogenous chymotrypsin-like enzyme(s) or related substances in receptor-mediated endocytosis of insulin.

show abstract

Effects of monensin on insulin processing in adipocytes. Evidence that the internalized insulin-receptor complex has some physiological activities.

Cited by 41 publications

References 38 publications

Insulin receptor internalization defect in an insulin-resistant mouse melanoma cell line

Insulin receptor internalization defect in an insulin-resistant mouse melanoma cell line

The β2-adrenergic receptors of human epidermoid carcinoma cells bear two different types of oligosaccharides which influence expression on the cell surface

Chymotrypsin substrate analogues inhibit endocytosis of insulin and insulin receptors in adipocytes.

Contact Info

Product

Resources

About