Biochemical and functional characterization of the rat liver glucose-transport system Comparisons with the adipocyte glucose-transport system

Ciaraldi, Theodore P.; Horuk, Richard; Matthaei, S.

doi:10.1042/bj2400115

Cited by 66 publications

(40 citation statements)

References 42 publications

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“…This mechanism for stimulation of glucose transport was later shown to be operative in other insulin target tissues such as rat diaphragm (15) and heart (16), but not in cells lacking an insulin response, such as hepatocytes (17). We (18) and others (19) have also demonstrated insulin-induced recruitment of transporters in human adipocytes.…”

Section: Introductionmentioning

confidence: 93%

Role of glucose transporters in the cellular insulin resistance of type II non-insulin-dependent diabetes mellitus.

Garvey¹,

Huecksteadt²,

Matthaei³

et al. 1988

J. Clin. Invest.

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174

109

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To examine the role of glucose transport proteins in cellular insulin resistance, we studied subcutaneous adipocytes isolated from lean control, obese control (body mass index [BMII 33.4±0.9), and untreated obese non-insulin-dependent diabetes mellitus (NIDDM) patients (BMI 35.2±2.1; fasting glucose 269±20 mg/dl). Glucose transporters were measured in plasma membrane (PM), low-density (LDM), and high-density (HDM) microsomal subfractions from basal and maximally insulin-stimulated cells using the cytochalasin B binding assay, and normalized per milligram of membrane protein. In all subgroups, insulin led to an increase in PM glucose transporters and a corresponding depletion of transporters in the LDM. Insulin recruited 20% fewer transporters to the PM in the obese subgroup when compared with lean controls, and this was associated with a decline in LDM transporters with enlarging cell size in the control subjects. In NIDDM, PM, and LDM, transporters were decreased 50% in both basal and stimulated cells when compared with obese controls having similar mean adipocyte size. Cellular depletion of glucose transporters was not the only cause of insulin resistance, because the decrease in rates of '4Cj-D-glucose transport (basal and insulin-stimulated) was greater than could be explained by reduced numbers of PM transporters in both NIDDM and obesity. In HDM, the number of transporters was not influenced by insulin and was similar in all subgroups. We conclude that (a) in NIDDM and obesity, both reduced numbers and impaired activity of glucose transporters contribute to cellular insulin resistance, and (b) in NIDDM, more profound cellular insulin resistance is associated primarily with a further depletion of cellular transporters.

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Section: Introductionmentioning

confidence: 93%

Role of glucose transporters in the cellular insulin resistance of type II non-insulin-dependent diabetes mellitus.

Garvey¹,

Huecksteadt²,

Matthaei³

et al. 1988

J. Clin. Invest.

Self Cite

174

109

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“…If this is the case, control of the glucose transporter would be more complex than had hitherto been envisioned, with different isozymes of the transporter being under different mechanisms of regulation. These may be related to tissuespecific differences in glucose transport and may have different biochemical properties and physiological roles; for example, it has been reported that there is biochemical and functional heterogeneity in rat adipocyte glucose transporters (12) and that there are biochemical and functional differences in the hepatic and adipocyte glucose transporters (5). Changes in the expression of glucose transporter isozymes might account for differences in the Michaelis constants for hexose transport associated with certain tumors (28,29).…”

Section: Methodsmentioning

confidence: 99%

Transformation by the src oncogene alters glucose transport into rat and chicken cells by different mechanisms.

White

Weber

1988

Mol. Cell. Biol.

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Transformation of both rat and chicken fibroblasts by the src oncogene leads to a four-to fivefold increase in the rate of glucose transport and in the level of the glucose transporter protein. We have previously shown that, with chicken embryo fibroblasts, transformation leads to a reduction in the rate of degradation of the transporter, with little or no increase in the rate of its biosynthesis. We now show that, with the rat-1 cell line, the opposite result was obtained. src-induced transformation led to an increase in transporter biosynthesis, with little effect on turnover. A src-induced increase in transporter mRNA entirely accounted for the increase in biosynthesis of the protein. By contrast, in chicken embryo fibroblasts, the level of transporter mRNA was low and was not induced to rise by src transformation. Thus, src induced an increase in the level of the glucose transport protein by fundamentally different mechanisms in chicken embryo fibroblasts and rat-1 cells. To test whether this difference was due to rat-1 cells being an immortalized cell line, we measured transporter mRNA levels in primary fibroblast cultures from rat embryos and in parallel cultures transformed by src. Transporter mRNA was inducible by src in these cells. Thus, the difference in mRNA inducibility between chicken and rat cells is not due to immortalization.Malignant transformation of chicken and rat embryo fibroblasts by Rous sarcoma virus (RSV) results in a marked increase in the rate of hexose transport across the plasma membrane (11,14,15,17,26,27). In cells transformed by RSV mutants in which the transforming protein pp60j-fsrc is temperature sensitive, the increase in transport is also temperature sensitive, indicating that the activity of pp6Ovsrc is necessary for both establishing and maintaining the transport alteration (14,15,17). It is generally accepted that the enhancement of transport is due to an increased number of hexose transporter molecules at the cell membrane, rather than a modification of existing carriers, for the following reasons. (i) Kinetic evidence indicates that the Vmax for transport is increased (7,14,15,26,27 biosynthesis showed that there was little or no difference between normal and transformed cells (22).In contrast, results obtained by others using rodent cells indicate that src transformation induces increased glucose transport by elevating the level of the mRNA for the transporter (8). To resolve this apparent discrepancy, we measured the effects of src transformation on the levels of transporter mRNA, transporter biosynthesis, and transporter degradation in chicken embryo fibroblasts, rat-i cells, and primary cultures of fibroblasts explanted from a rat embryo. We concluded that src increases the level of transporter by mechanisms that differ between rat and chicken cells. In the former, src elevates transporter mRNA levels and biosynthesis, whereas in the latter this is not the case and src acts to inhibit transporter turnover. 2) and stored at -20°C. Lysates were cleared by centrifugati...

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“…Hepatocytes do possess high glucose transport activity, but this transport system can be distinguished from GT because of its higher Km and decreased sensitivity to cytochalasin B (21). Upon long exposure, autoradiographs of RNA blots reveal a faint band after hybridization with a GT probe (4,22); however, it remains to be determined whether this signal arises from hepatocytes and, if so, whether it is due to a liver-specific glucose transporter.…”

mentioning

confidence: 94%

Evidence for expression of the facilitated glucose transporter in rat hepatocytes.

Rhoads

Takano

Gattoni‐Celli

et al. 1988

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

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The eukaryotic facilitated glucose transporter (GT) is expressed by many cell types, with the notable exception of hepatocytes; however, GT is expressed by several hepatoma cell lines, including the well-differentiated lines Fao, Hep3B, and HepG2. We report on studies carried out to determine the aspect(s) of the transformed phenotype that might be responsible for activating GT expression. Using RNA blot analysis with probes derived from rat GT cDNA, we found that GT was expressed by rat hepatocytes under two conditions (i) in vitro, when isolated hepatocytes were placed in cell culture, and (a) in vivo, when rats were subjected to starvation for .2 days. However, GT expression was not an obligatory feature of hepatomas, since two primary hepatocellular carcinomas did not express any GT mRNA. GT expression in hepatocytes was reduced by addition of dimethyl sulfoxide or sodium butyrate to the culture medium. Since these reagents are known to promote differentiation in some cell culture systems, their effect on hepatocytes may be to maintain the GT repression normally observed in vivo. Inclusion or exclusion in the culture medium of several other agents that enhance hepatocyte viability (serum, insulin, corticosteroids, epidermal growth factor, or triiodothyronine) did not affect GT expression. It is unclear whether the two conditions that led to GT expression in hepatocytes are related by a common signaling mechanism. Possibly, both cases involve a "stress" response: in vivo, a normal physiological response to starvation; in vitro, a response to a major alteration in the cellular environment.

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Biochemical and functional characterization of the rat liver glucose-transport system Comparisons with the adipocyte glucose-transport system

Cited by 66 publications

References 42 publications

Role of glucose transporters in the cellular insulin resistance of type II non-insulin-dependent diabetes mellitus.

Role of glucose transporters in the cellular insulin resistance of type II non-insulin-dependent diabetes mellitus.

Transformation by the src oncogene alters glucose transport into rat and chicken cells by different mechanisms.

Evidence for expression of the facilitated glucose transporter in rat hepatocytes.

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