Transport and metabolism of glucose in an insulin-secreting cell line, .beta.TC-1

Whitesell, Richard R.; Powers, Alvin C.; Regen, David M.; Abumrad, Nada A.

doi:10.1021/bi00113a011

Cited by 28 publications

(31 citation statements)

References 32 publications

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“…We have also observed retention of tritium (10-3 0%) in me tabolites from [2-3H]glucose in the BFC-l brown fat cell line (Whitesell RR and Abumrad NA, un published results). In contrast, no persistence of tri tiated products was noted in liver (Malaisse et a!., 1988), frog oocytes (Whitesell et a!., 1993), or a cul tured pancreatic beta cell line (I3TC) (Whitesell et a!., 1991). Whereas release of 3H20 from [2-3H]glu cose reflects the activity of the phosphorylation step (Katz and Dunn, 1967 ;Liemans et a!., 1989 ; Manuel y Keenoy et a!., 1992), it does not necessarily correspond to the total rate of glucose utili zation.…”

Section: Discussionmentioning

confidence: 99%

Coupled Glucose Transport and Metabolism in Cultured Neuronal Cells: Determination of the Rate-Limiting Step

Whitesell

Ward

McCall

et al. 1995

J Cereb Blood Flow Metab

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Summary: 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 pro cesses 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 in tracellular 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 intra- 814 cellular glucose pool in a parallel assay, rates of glucose efflux were three-to-fivefold greater than rates of phos phorylation. 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 trans port. In contrast to results with glucose, both cell types accumulated 2-deoxY-D-[1 4 C)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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Section: Discussionmentioning

confidence: 99%

Coupled Glucose Transport and Metabolism in Cultured Neuronal Cells: Determination of the Rate-Limiting Step

Whitesell

Ward

McCall

et al. 1995

J Cereb Blood Flow Metab

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“…Efrat and co-workers [16] have produced a series of such lines known generally as TC-3 exhibited some GSIS, but were found to be maximally stimulated at concentrations of glucose well below the physiological range. These lines were later found to have high levels of the low K m glucose transporter GLUT1 and elevated low K m hexokinase activity [18,19]. Subsequently, newly isolated lines such as b TC-6 and b TC-7 were shown to have a GSIS response that resembled that of the islet in magnitude and concentration dependence [19].…”

Section: : S 42-s 47]mentioning

confidence: 99%

“…Cell lines derived by transgenic expression of T-antigen in beta-cells exhibit variable phenotypes [16][17][18][19]. In some cases, these differences have been correlated with expression of glucose transporters and glucose phosphorylating enzymes.…”

Section: : S 42-s 47]mentioning

confidence: 99%

Engineered cell lines for insulin replacement in diabetes: current status and future prospects

Newgard

Clark²,

BeltrandelRio

et al. 1997

Diabetologia

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The recently concluded diabetes control and complications trial (DCCT) [1] has emphatically underscored the potential for improvement in current treatment protocols for diabetes mellitus. 'Conventional' insulin therapy, involving 1-2 injections of the hormone per day and intermittent glucose monitoring is clearly not as effective at slowing the progression of the debilitating and costly secondary complications of the disease as 'tight control', in which insulin pumps or multiple injections are combined with frequent glucose monitoring to limit hyperglycaemic excursions. Unfortunately, improvement in glycaemic control through increased insulin dosing requires a new level of compliance and discipline, and places the patient at significantly enhanced risk for dangerous hypoglycaemic episodes. These concerns have produced a surprising reticence among both physicians and patients towards implementation of tight control therapy. This reaction has served to place a new emphasis on the design of better methods for insulin replacement in insulin-dependent diabetes mellitus (IDDM). A primary consideration in such work is to develop a 'closed loop' system in which the hormone is delivered in response to metabolic demand, thereby eliminating the need for self monitoring by the patient. Three basic approaches to achieving this end have been contemplated, and are being investigated with ever increasing vigour. The first involves development of mechanical devices consisting of a pump or other mechanism for insulin delivery linked to a detector system for blood glucose. The second involves transplantation of insulin-producing cells from human or large mammal donors into IDDM patients. This can be achieved by transplantation of the entire pancreas or isolated pancreatic islets. Because of the difficulty and cost associated with islet isolation and pancreas transplantation, a third approach has emerged, in which the tools of molecular biology are used to fashion insulin-secreting cell lines with fuelmediated insulin secretion responses resembling Diabetologia (1997) Summary The recently completed diabetes complications and control trial has highlighted the need for improvement of insulin delivery systems for treatment of insulin-dependent diabetes mellitus. Despite steady improvement in methods for islet and whole pancreas transplantation over the past three decades, the broad-scale applicability of these approaches remains uncertain due in part to the difficulty and expense associated with procurement of functional tissue. To address this concern, we and others have been using the tools of molecular biology to develop cell lines with regulated insulin secretion that might serve as a surrogate for primary islets or pancreas tissue in transplantation therapy. This article seeks to provide a brief summary of the current status of this growing field, with a particular emphasis on progress in producing cell lines with appropriate glucose-stimulated insulin secretion. [Diabetologia (1997) 40: S 42-S 47]

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“…Figure 10 shows how the intracellular glucose concentration G in depends on the extracellular glucose concentration G 0 . Shown together with the experimental results [28] are the saturated values of G in obtained from simulations with G 0 varied from 1 mM to 26 mM. It is pleasing to see the excellent agreement between the experimental data and the simulation data.…”

Section: Simulation Resultsmentioning

confidence: 69%

“…To probe bursting patterns in this stationary state, we set the insulin flow rate k 0 = 9.2 s −1 , maintaining previous values of other parameters. Such a low insulin feedback condition may correspond to the experiment performed to obtain stationary values of the intracellular glucose concentration at several extracellular glucose concentrations [28]. The resulting behavior of the membrane potential is displayed in Fig.…”

Section: Simulation Resultsmentioning

confidence: 90%

Glucose metabolism and oscillatory behavior of pancreatic islets

Kang

Kim

et al. 2005

Phys. Rev. E

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A variety of oscillations are observed in pancreatic islets. We establish a model, incorporating two oscillatory systems of different time scales: One is the well-known bursting model in pancreatic β-cells and the other is the glucose-insulin feedback model which considers direct and indirect feedback of secreted insulin. These two are coupled to interact with each other in the combined model, and two basic assumptions are made on the basis of biological observations: The conductance g K(AT P ) for the ATP-dependent potassium current is a decreasing function of the glucose concentration whereas the insulin secretion rate is given by a function of the intracellular calcium concentration. Obtained via extensive numerical simulations are complex oscillations including clusters of bursts, slow and fast calcium oscillations, and so on. We also consider how the intracellular glucose concentration depends upon the extracellular glucose concentration, and examine the inhibitory effects of insulin.

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Transport and metabolism of glucose in an insulin-secreting cell line, .beta.TC-1

Cited by 28 publications

References 32 publications

Coupled Glucose Transport and Metabolism in Cultured Neuronal Cells: Determination of the Rate-Limiting Step

Coupled Glucose Transport and Metabolism in Cultured Neuronal Cells: Determination of the Rate-Limiting Step

Engineered cell lines for insulin replacement in diabetes: current status and future prospects

Glucose metabolism and oscillatory behavior of pancreatic islets

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