Evidence That Downregulation of Hexose Transport Limits Intracellular Glucose in 3T3-L1 Fibroblasts

Whitesell, Richard R.; Regen, David M.; Pelletier, Diana; Abumrad, Nada A.

doi:10.2337/diab.39.10.1228

Cited by 10 publications

(1 citation statement)

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“…The concentration of free 2-deoxyglucose present inside the cell at equilibrium was calculated using relationships presented by Regen and Morgan ( 1964) abi P ity to phosphorylate 2-deoxyglucose. and recently defined for the 3T3-Ll fibroblasts by Whitesell et al, (1990).…”

Section: Determination Of 2-deoxyglucose Uptakementioning

confidence: 99%

Regulation of glucose transport as well as glucose transporter and immediate early gene expression in 3T3‐L1 preadipocytes by 8‐bromo‐cAMP

Cornelius

Marlowe

Call

et al. 1991

Journal Cellular Physiology

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In the present study we have examined the ability of 8-bromoadenosine cyclic 3',5'-phosphate (8-bromo-cAMP; the membrane permeant analog of cAMP which can activate protein kinase A) to mimic hormone action and stimulate glucose transport and glucose transporter (GLUT-1) gene expression as well as the expression of several growth-related protooncogenes in quiescent 3T3-L1 fibroblasts. 8-Bromo-cAMP induced a rapid and prolonged increase in the rate of hexose transport. Early activation of hexose transport (within 30 min) was associated with increased plasma membrane immunoreactive glucose transporters, which corresponded to a doubling in the number of D-glucose-displaceable, plasma membrane cytochalasin B binding sites. The time course for 8-bromo-cAMP-induced hexose transport preceded the accumulation of GLUT-1 mRNA, which peaked between 4 and 8 h after exposure to the agent, and subsequently declined to approach basal (control) levels. Expression of the immediate-early genes c-fos and jun-B was induced by 8-bromo-cAMP on a rapid, but sustained time course, whereas induction of c-jun expression was delayed. Alterations in specific mRNAs following exposure to 8-bromo-cAMP were due to increased gene transcription (as judged by nuclear transcription run-on assays), although with respect to GLUT-1, an increase in mRNA stability was also observed. Treatment of the cells with forskolin resulted in the induction of GLUT-1 expression as well as expression of the immediate early genes. Exposure of quiescent 3T3-L1 fibroblasts to 8-bromo-cAMP resulted in a substantial increase in rates of total protein and RNA synthesis, but had little effect on DNA synthesis. The results demonstrate that 8-bromo-cAMP initiated a G0/G1 transition, but did not permit progression into S-phase. The results further suggest that increased cytosolic cAMP results in the stimulation of glucose transport by three distinct mechanisms to include translocation of pre-existing transporters, increased transcription of the GLUT-1 gene and increased stability of GLUT-1 mRNA.

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Section: Determination Of 2-deoxyglucose Uptakementioning

confidence: 99%

Regulation of glucose transport as well as glucose transporter and immediate early gene expression in 3T3‐L1 preadipocytes by 8‐bromo‐cAMP

Cornelius

Marlowe

Call

et al. 1991

Journal Cellular Physiology

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Differential Glucose Uptake in Retina- and Brain-Derived Endothelial Cells

Rajah

Olson

Grammas

2001

Microvascular Research

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Glucose transporter gene expression in rat conceptus during high glucose culture

et al. 1993

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We investigated the expression of glucose transporter genes and protein in embryo and yolk sac during organogenesis and the regulation of glucose transporters during culture in hyperglycaemic media. Erythrocyte-type glucose transporter (GLUT 1) and brain-type glucose transporter (GLUT 3) mRNA were expressed in embryo and yolk sac. The expression of GLUT-1 and GLUT-3 mRNA was abundant on day 9-11 and day 9-10 in the embryo, respectively, and day 9-14 and day 10-11 in the yolk sac, respectively. The levels of GLUT-1 protein in the embryo increased in parallel with the expression of GLUT-1 mRNA during the corresponding period. Immunohistochemical staining of GLUT-1 protein was found principally in the neuroepithelial cells surrounding the neural tube in the embryo on day 10 and appeared in the microvessels surrounding the neural tube after day 12. To test whether the expression of glucose transporter genes and protein was suppressed during hyperglycaemia, conceptuses were cultured in high glucose medium. The abundant expression of GLUT-1 protein was not decreased during culture in high glucose media for 24 h (day 9-10) and was only down-regulated by prolonged exposure to this media for 48 h (day 9-11). We have demonstrated the predominant expression of the high affinity glucose transporter (GLUT 1 and GLUT 3) genes and (GLUT 1) protein in embryo during the early period of organogenesis. The persistently abundant expression of glucose transporter during the critical period of neural tube formation (day 9-10) even in the presence of hyperglycaemia may explain one of the mechanism of increased glucose flux into the neuroepithelium, which may lead to neural tube defects.

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Evidence That Downregulation of Hexose Transport Limits Intracellular Glucose in 3T3-L1 Fibroblasts

Cited by 10 publications

References 0 publications

Regulation of glucose transport as well as glucose transporter and immediate early gene expression in 3T3‐L1 preadipocytes by 8‐bromo‐cAMP

Regulation of glucose transport as well as glucose transporter and immediate early gene expression in 3T3‐L1 preadipocytes by 8‐bromo‐cAMP

Differential Glucose Uptake in Retina- and Brain-Derived Endothelial Cells

Glucose transporter gene expression in rat conceptus during high glucose culture

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