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On the mechanism by which noradrenaline increases the activity of phosphofructokinase in isolated rat adipocytes.

ABSTRACT: We confirmed that, as reported by Sooranna & Saggerson [(1982) Biochem. J. 202, 753-758], the affinity of 6-phosphofructo-1-kinase (PFK) for fructose 6-phosphate in an adipocyte extract was increased after incubation of the cells in the presence of noradrenaline. The participation of fructose 2,6-bisphosphate in this kinetic modification could be excluded, because the noradrenaline effect persisted after extensive gel filtration of the extracts and also because the treatment did not cause any change in the concentration of fructose 2,6-bisphosphate in the adipocytes. Oleic acid was found to be another potent positive effector of PFK in an adipocyte extract, with a Ka of 10 microM. Its effect was synergistic with that of fructose 2,6-bisphosphate and AMP, and was counteracted by serum albumin. Palmitic acid had a similar effect. We conclude that the large increase in fatty acid concentration caused by noradrenaline treatment is an explanation for the activation of phosphofructokinase at low fructose 6-phosphate concentrations in an adipocyte extract.

SUBMITTER: Lederer B

PROVIDER: S-EPMC1153272 | biostudies-other | 1984 Feb

REPOSITORIES: biostudies-other

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Project description:Glucose uptake into brown adipose tissue has been shown to be enhanced directly by noradrenaline (norepinephrine) released from sympathetic nerves. In this study we characterized the glucose transport system in cultured brown adipocytes, which responds to noradrenaline as well as insulin, and analysed the mechanism underlying the noradrenaline-induced increase in glucose transport. Insulin increased 2-deoxyglucose (dGlc) uptake progressively at concentrations from 10(-11) to 10(-6) M, with maximal stimulation at 10(-7) M. Noradrenaline concentrations ranging from 10(-8) to 10(-6) M also enhanced dGlc uptake, even in the absence of insulin. The effects of noradrenaline and insulin on dGlc uptake were additive. The stimulatory effect of noradrenaline was mimicked by the beta3-adrenergic agonist, BRL37344, at concentrations two orders lower than noradrenaline. Dibutyryl cyclic AMP also mimicked the stimulatory effect of noradrenaline, and the antagonist of cyclic AMP, cyclic AMP-S Rp-isomer, blocked the enhancement of glucose uptake due to noradrenaline. Furthermore Western blot analysis with an anti-phosphotyrosine antibody revealed that, in contrast with insulin, noradrenaline apparently does not stimulate intracellular phosphorylation of tyrosine, suggesting that the noradrenaline-induced increase in dGlc uptake depends on elevation of the intracellular cyclic AMP level and not on the signal chain common to insulin. When cells were incubated with insulin, the content of the muscle/adipocyte type of glucose transporter (GLUT4) in the plasma membrane increased, with a corresponding decrease in the amount in the microsomal membrane. In contrast, noradrenaline did not affect the subcellular distribution of GLUT4 or that of the HepG2/erythrocyte type of glucose transporter. Although insulin increased Vmax. and decreased the Km value for glucose uptake, the effect of noradrenaline was restricted to a pronounced decrease in Km. These results suggest that the mechanism by which noradrenaline stimulates glucose transport into brown adipocytes is not due to translocation of GLUT but is probably due to an increase in the intrinsic activity of GLUT, which is mediated by a cyclic AMP-dependent pathway.

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On the mechanism by which noradrenaline increases the activity of phosphofructokinase in isolated rat adipocytes.

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