Insulin activates the appearance of insulin-like growth factor II receptors on the adipocyte cell surface.

Oka, Yoshitomo; Mottola, Cristina; Oppenheimer, C L; Czech, Michael P.

doi:10.1073/pnas.81.13.4028

Cited by 121 publications

(49 citation statements)

References 33 publications

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“…It has been shown by ligand binding studies that insulin causes translocation of IGF-II/Man-6-P receptors from an intracellular storage pool to the cell surface without increasing their affinity for IGF-II (18,19,32). Also, insulin stimulates internalization and degradation of IGF-II, whereas IGF-II itself does not have this effect (27).…”

Section: Discussionmentioning

confidence: 99%

“…I-IGF-II binding studies (18,19,23), insulin causes a translocation from LM to PM fractions of a small portion of the IGF-II/ Man-6-P receptor in such a way that its amount in LM decreases to 67% and increases in PM to 20% of the total receptor content. The amount of this receptor in heavy microsomes does not change in response to insulin.…”

Section: Methodsmentioning

confidence: 99%

“…The 10 -15% of the total IGF-II/Man-6-P receptors that is found co-localized with GLUT4 comprises the entire population of the receptor that cycles to and from the cell surface in response to insulin. In other words, the previously described insulin-dependent translocation of IGF-II/Man-6-P receptor to the cell surface (18,19) goes exclusively through GLUT4-containing compartments. Taken together with previously published data, we postulate that the glucose transporting machinery, that is, GLUT4-containing vesicles in unstimulated adipocytes, may represent a specialized compartment that accumulates a number of recycling proteins and mediates their translocation to the cell surface in an insulin-sensitive fashion.…”

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confidence: 99%

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The Insulin-like Growth Factor II/Mannose 6-Phosphate Receptor Utilizes the Same Membrane Compartments as GLUT4 for Insulin-dependent Trafficking to and from the Rat Adipocyte Cell Surface

Kandror

Pilch

1996

Journal of Biological Chemistry

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The insulin-like growth factor II (IGF-II)/mannose 6-phosphate (Man-6-P) receptor recycles in adipose cells between the cell surface and an intracellular storage pool, and the rate of this trafficking is markedly enhanced by insulin. We show here that the IGF-II/Man-6-P receptor is a constituent of the GLUT4-containing compartment ("GLUT4 vesicles") where it represents gp230, a major recycling protein detected earlier by cell surface biotinylation (Kandror, K. V., and Pilch, P. F. (1994) J. Biol. Chem. 269, 138 -142). The GLUT4 vesicles include 10 -15% of the total and all of the acutely insulin-responsive recycling population of the IGF-II/Man-6-P receptor. The main part of the IGF-II/Man-6-P receptor population is excluded from the pathway of GLUT4 trafficking and either resides permanently in intracellular membranes or has a much slower rate of cycling to the cell surface. Thus, GLUT4 vesicles mediate the insulindependent delivery to the cell surface of the IGF-II/Man-6-P receptor as well as the other recyclable proteins with extracellular functional domains (GLUT4 and the aminopeptidase gp160).In adipocytes and in skeletal muscle, insulin causes the tissue-specific glucose transporter isoform, GLUT4, to translocate to the cell surface from an intracellular storage pool (1-5). The amount of GLUT4 translocated to the plasma membrane in response to insulin corresponds very well to the increased rate of glucose uptake, particularly in fat cells where these two parameters can be most easily measured (4). Therefore, GLUT4 translocation appears to account for the majority if not all of the insulin-dependent increased glucose uptake required for postprandial blood glucose homeostasis. The mechanism of this process has been extensively studied, both for fundamental questions of cell biology and for its possible relevance to diabetes mellitus (for recent reviews, see Refs. 6 -10). A major unresolved question concerning the GLUT4 translocation process concerns the identification and characterization of the membrane compartments utilized by GLUT4 as it cycles to and from the cell surface. The limited information available on this topic comes from immunoelectron microscopy studies in delipidated brown adipose cells (11) as well as in white adipocytes (12).Both studies showed that under basal conditions, most of the intracellular GLUT4 is present in vesicles and short tubules near the cell surface, and insulin administration depletes intracellular GLUT4 by redistributing it to the plasma membrane. Slot et al. (11) also showed that cellular insulin exposure led to some GLUT4 localization in early endosomes as marked by albumin uptake. These studies left open the question as to whether other proteins followed the same trafficking pathway as GLUT4.Recent work from our lab and elsewhere has begun to address this question. Using cell surface biotinylation of insulintreated adipocytes followed by immunoadsorption of GLUT4-containing membranes, we identified three glycoproteins (gp) 1 of molecular masses 110, 160, and 230 kilod...

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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The Insulin-like Growth Factor II/Mannose 6-Phosphate Receptor Utilizes the Same Membrane Compartments as GLUT4 for Insulin-dependent Trafficking to and from the Rat Adipocyte Cell Surface

Kandror

Pilch

1996

Journal of Biological Chemistry

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“…Recent studies by Lawrence et al ( 13) and others (25) suggested that the okadaic acid-induced inhibition oftranslocation ofGLUT-4 is due to increased reinternalization of GLUT-4 in a phosphorylated form. Studies by Corvera and Czech (32) and others (33,34) showed that the insulin-like growth factor II (IGF II) receptor is translocated to the plasma membrane in response to insulin. Moreover, insulin causes a decrease in IGF II receptor phosphorylation in the plasma membranes.…”

Section: Discussionmentioning

confidence: 99%

Effect of streptozotocin-induced diabetes on GLUT-4 phosphorylation in rat adipocytes.

Begum¹,

Draznin²

1992

J. Clin. Invest.

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We have examined the regulation of GLUT4 phosphorylation in adipocytes isolated from diabetic rats. Despite progressive (40-70%) reductions in GLUT4 protein contents on the 2nd, 7th, and 14th day of diabetes, the phosphorylation of GLUT4 was increased two-to fourfold. These alterations were accompanied by concomitant reductions (40-66%) in the insulin-stimulated 2-deoxyglucose transport. Insulin treatment of diabetic animals for 5 d restored glucose transport activity, GLUT4 protein, and GLUT4 phosphorylation to control levels whereas vanadate and phlorizin were ineffective. In control adipocytes, insulin promoted GLUT4 translocation from the low density microsomal (LDM) pool to the plasma membranes (PM) and decreased the state of GLUT4 phosphorylation. In adipocytes isolated from the diabetic rats, insulin failed to stimulate GLUT4 translocation and to decrease GLUT4 phosphorylation. To explore the mechanism of the diabetes-induced increases in the GLUT4 phosphorylation, we investigated phosphoserine phosphatase (PSPase) activities using 32P-labeled GLUT4 and phosphorylase "a" as substrates. Diabetes resulted in 50-60% increase in the particulate PSPase activity and concomitant reductions in cytosolic PSPase activities. Although reduced cytosolic PSPase activity correlated with an inadequate dephosphorylation of LDM GLUT4, the existence of highly phosphorylated PM GLUT4 in the presence of increased particulate PSPase activity required additional explanation. To address this problem, we used PM GLUT4 from diabetic rats as a substrate of particulate PSPase. Highly active diabetic particulate PSPase, which dephosphorylated control GLUT4 and phosphorylase a, failed to dephosphorylate PM GLUT4 from diabetic rats. These data suggest that PM GLUT4 from diabetic rats is unable to interact with PSPase or that its phosphorylation sites are not accessible to PSPase action. In summary, an induction of diabetes with streptozotocin resulted in significant increases in GLUT4 phosphorylation.In contrast to normal cells, insulin failed to promote GLUT4 recruitment to the plasma membranes and its dephosphorylation in diabetic adipocytes. At the same time, diabetes appears to induce redistribution of PSPases, resulting in lower cytosolic activity and higher particulate activity. It also appears that the existence of highly phosphorylated GLUT4 in the plasma membranes of diabetic adipocytes resulted from its inability to

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“…Insulin also stimulates the net exocytosis of the cationindependent mannose-6-phosphate receptor (CI͞M6PR), which is located in a distinct vesicular compartment (31,32). CI͞M6PR traffics between the trans-Golgi network, late endosomes, and lysosomes, distinct from the GLUT4͞IRAP-containing compartments (33).…”

Section: Overexpression Of Cap⌬soho In 3t3-l1 Adipocytes Specificallymentioning

confidence: 99%

The sorbin homology domain: A motif for the targeting of proteins to lipid rafts

Kimura

Baumann

Chiang

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

140

157

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On phosphorylation of Cbl, the c-Cbl-associated protein (CAP)͞Cbl complex dissociates from the insulin receptor and translocates to a lipid raft membrane fraction to form a ternary complex with flotillin. Deletion analyses of the CAP gene identified a 115-aa region responsible for flotillin binding. This region is homologous to the peptide sorbin and is referred to as the sorbin homology (SoHo) domain. This domain is present in two other proteins, vinexin and ArgBP2. Vinexin also interacted with flotillin, and deletion of its SoHo domain similarly blocked flotillin binding. The overexpression of a CAP mutant in which the SoHo domain had been deleted (CAP⌬SoHo) prevented the translocation of Cbl to lipid rafts and subsequently blocked the recruitment of CrkII and C3G. Moreover, overexpression of CAP⌬SoHo prevented the stimulation of glucose transport and GLUT4 translocation by insulin. These results suggest a mechanism for localization of signaling proteins to the lipid raft that mediates the compartmentalization of crucial signal transduction pathways.L ipid rafts are microdomains of the plasma membrane enriched in cholesterol and sphingolipids (1, 2). These regions concentrate certain signaling molecules (3, 4), including heterotrimeric and small G proteins (5-7), Src-family tyrosine kinases (8, 9), endothelial nitric oxide synthase (10, 11), G-proteincoupled receptors (12), and certain tyrosine kinase receptors (13). This concentration of signaling molecules suggests that these microdomains might function as a site for compartmentalization of signaling events. We observed that insulin stimulated the tyrosine phosphorylation of c-Cbl (14) and its subsequent translocation to a caveolin-enriched, lipid raft membrane fraction (15, 16). The c-Cbl-associated protein (CAP)͞Cbl complex interacts with the insulin receptor and dissociates after insulin stimulation, subsequently migrating to rafts because of the interaction of CAP with the lipid raft-associated protein flotillin (17)(18)(19). Moreover, the localization of the Cbl͞CAP complex to this microdomain recruits the guanyl nucleotide exchange protein C3G, resulting in the activation of the G protein TC10. This activation of TC10 generates a PI 3-kinaseindependent signal that is crucial to the regulation of glucose uptake by insulin (20,21).CAP is a multifunctional adapter protein with three SH3 domains in its C terminus and a region of homology to the gut peptide sorbin in its N terminus. The overall sorbin homology (SoHo)͞SH3 organization of CAP is also found in other proteins, including vinexin␣ and ArgBP2A. The similar organization of these proteins suggests that they may similarly function as adapters, linking signaling or cytoskeletal proteins to the lipid raft. We demonstrate here that the SoHo domain does indeed mediate the interaction of CAP and vinexin with flotillin. Moreover, this interaction is crucial for the localization of SH3-binding proteins such as Cbl to the lipid raft and propagation of the downstream signal. These data suggest a signaling par...

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Insulin activates the appearance of insulin-like growth factor II receptors on the adipocyte cell surface.

Cited by 121 publications

References 33 publications

The Insulin-like Growth Factor II/Mannose 6-Phosphate Receptor Utilizes the Same Membrane Compartments as GLUT4 for Insulin-dependent Trafficking to and from the Rat Adipocyte Cell Surface

The Insulin-like Growth Factor II/Mannose 6-Phosphate Receptor Utilizes the Same Membrane Compartments as GLUT4 for Insulin-dependent Trafficking to and from the Rat Adipocyte Cell Surface

Effect of streptozotocin-induced diabetes on GLUT-4 phosphorylation in rat adipocytes.

The sorbin homology domain: A motif for the targeting of proteins to lipid rafts

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