THE UPTAKE OF GLUCOSE INTO CELLS AND THE ROLE OF INSULIN IN GLUCOSE TRANSPORT

1964 ◽  
Vol 42 (6) ◽  
pp. 933-944 ◽  
Author(s):  
Margaret J. Henderson

This presentation has been restricted to the role of insulin in glucose transport in muscle cells and deals mainly with experiments using the perfused rat heart. The several possible means for glucose transfer into cells, diffusion, pores, pinocytosis, carriers, and dimerization, have been discussed; and arguments in favor of the carrier theory, namely, specificity, kinetics, inhibition, competition, and counterflow, have been elaborated. Glucose uptake has been considered to consist of three sequential steps: (1) passage of glucose from within the capillary to the cell surface, (2) transport across the cell membrane, and (3) metabolism of glucose within the cell. The first is considered to take place by diffusion and not to be significantly limiting under normal conditions, nor to be influenced by insulin. Transport across the cell membrane is thought to be mainly under the control of insulin and is the major rate-limiting step in glucose uptake when the extracellular glucose levels are in the normal range. Metabolism of glucose within the cell is the major rate-limiting step in glucose uptake when intracellular glucose concentration is so high that its phosphorylation is near saturation.

1986 ◽  
Vol 250 (1) ◽  
pp. E100-E102 ◽  
Author(s):  
K. Kubo ◽  
J. E. Foley

To determine the glucose and insulin concentrations at which glucose transport is rate limiting for insulin-mediated glucose uptake and metabolism in muscle, glucose clearance was determined in the presence of glucose concentrations ranging from trace to 20 mM and in the absence or presence of insulin in the perfused rat hindlimb. In the absence of insulin and at submaximally stimulating insulin concentrations glucose clearance was constant up to 7 mM glucose and then decreased as the glucose concentration was raised. At maximally stimulating insulin concentrations glucose clearance was constant up to 2 mM glucose and then decreased. The decrease in glucose clearance between 2 and 7 mM glucose in the presence of maximally stimulating insulin concentrations could not be accounted for by competition among glucose molecules for the glucose transport system. The results suggest that at physiological glucose concentrations in the presence of maximally stimulating insulin concentrations the rate-limiting step for insulin-mediated glucose uptake and metabolism in muscle shifts from glucose transport to some step beyond transport.


1976 ◽  
Vol 156 (2) ◽  
pp. 477-480 ◽  
Author(s):  
D Herbert ◽  
H L Kornberg

Over a wide range of growth rates, two strains of Escherichia coli growing aerobically in continuous culture under glucose limitation utilized glucose at rates identical with those at which cells harvested from the chemostats transported [14C]glucose.


2013 ◽  
Vol 25 (2) ◽  
pp. 456 ◽  
Author(s):  
L. A. Hinds ◽  
C. H. Tyndale-Biscoe

The corpus luteum (CL) of the tammar wallaby is inhibited by prolactin during lactation and seasonal quiescence. In seasonal quiescence a daily transient pulse of prolactin (PRL) of less than 2 h duration is sufficient to maintain inhibition. We investigated whether the same inhibition applies in lactation and, if so, how. Our results show that inhibition of the CL during lactation is maintained by a transient pulse of prolactin once a day. They also show that the minimum time without a PRL pulse for the CL to escape inhibition is more than 48 h and less than 72 h. Nevertheless, some animals had a longer refractory period than 72 h, which was reflected in a longer interval to the progesterone peak and birth. These results support the previous conclusion that PRL exercises its effect on a rate-limiting step in progesterone synthesis and secretion rate from the CL, which precedes any increase in its mass. Therefore, we conclude that the role of PRL is to act as a luteostatic agent, an effect that is in marked contrast to its luteotrophic effect in many eutherian species, including rodents.


2009 ◽  
Vol 2 ◽  
pp. IJTR.S1022 ◽  
Author(s):  
Kazuhiro Nakamura ◽  
Hiroyuki Hasegawa

Serotonin (5-hydroxytryptamine [5-HT]) has been implicated in a variety of physiological and pathological functions. Multiple steps of enzyme reactions enable biosynthesis of 5-HT. The first and rate-limiting step of the reaction is the synthesis of 5-hydroxy- L-tryptophan (5-HTP) from L-tryptophan. This step is dictated by an enzyme, tryptophan hydroxylase (TPH). TPH requires 6R- L-erythro-5,6,7,8-tetrahydrobiopterin (BH4) as a co-substrate of TPH. 5-HTP has been simply regarded as a precursor of 5-HT and it is believed that the biological significance of 5-HTP is essentially ascribed to the production of 5-HT. However, recent works shed light on the specific functions of 5-HTP in the periphery. In this review article, we focus on the specific roles of exogenous 5-HTP as well as the endogenous 5-HTP in the gut epithelial cells. Since systemic treatment with 5-HTP is applied to patients with lower 5-HT levels, the studies on the specific role of 5-HTP might create an opportunity to explore the effects of exogenously-applied 5-HTP in the gut in man.


1995 ◽  
Vol 15 (5) ◽  
pp. 814-826 ◽  
Author(s):  
Richard R. Whitesell ◽  
Michael Ward ◽  
Anthony L. McCall ◽  
Daryl K. Granner ◽  
James M. May

In brain and nerves the phosphorylation of glucose, rather than its transport, is generally considered the major rate-limiting step in metabolism. Since little is known regarding the kinetic coupling between these processes in neuronal tissues, we investigated the transport and phosphorylation of [2-3H]glucose in two neuronal cell models: a stable neuroblastoma cell line (NCB20), and a primary culture of isolated rat dorsal root ganglia cells. When transport and phosphorylation were measured in series, phosphorylation was the limiting step, because intracellular glucose concentrations were the same as those outside of cells, and because the apparent Km for glucose utilization was lower than expected for the transport step. However, the apparent Km was still severalfold higher than the Km of hexokinase I. When [2-3H]glucose efflux and phosphorylation were measured from the same intracellular glucose pool in a parallel assay, rates of glucose efflux were three- to-fivefold greater than rates of phosphorylation. With the parallel assay, we observed that activation of glucose utilization by the sodium channel blocker veratridine caused a selective increase in glucose phosphorylation and was without effect on glucose transport. In contrast to results with glucose, both cell types accumulated 2-deoxy-d-[14C]glucose to concentrations severalfold greater than extracellular concentrations. We conclude from these studies that glucose utilization in neuronal cells is phosphorylation-limited, and that the coupling between transport and phosphorylation depends on the type of hexose used.


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