Regulation of glucose transport by pioglitazone in cultured muscle cells

El‐Kebbi, Imad M.; Roser, Susanne; Pollet, Robert J.

doi:10.1016/0026-0495(94)90173-2

Cited by 49 publications

(26 citation statements)

References 46 publications

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“…This is the only case in which pioglitazone has been found to reduce glucose metabolism, since all previous reports showed that this and other thiazolidinediones increase glucose uptake in cultured cells [9,16,17] and in vivo, as recently shown in the myocardium of diabetic patients [33]. In addition, pioglitazone did not reverse the decreases in CGU associated with overexpression of TGFβ1, despite the fact that this thiazolidinedione CGU (ratio to white matter) System CGU values are compared using three evaluations: (1) efficiently inhibits the inflammatory reaction in this model [8].…”

Section: Discussionmentioning

confidence: 91%

“…In vitro studies showing that pioglitazone increases glucose uptake and consumption in muscle cells [16], adipocytes [17] and astrocytes [9] have suggested that the capacity to stimulate glucose metabolism could be a general property of thiazolidinediones that is also applicable to the brain. Considering the strict dependence that the brain has on glucose as a fuel [15], a stimulatory action of thiazolidinediones on glucose metabolism would provide an additional therapeutic benefit in pathologies such as Alzheimer's disease.…”

Section: Introductionmentioning

confidence: 99%

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Pioglitazone does not increase cerebral glucose utilisation in a murine model of Alzheimer’s disease and decreases it in wild-type mice

2006

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Aims/hypothesis Clinical trials are in progress to test thiazolidinediones in neurodegenerative diseases such as Alzheimer's disease that involve deficiencies in brain glucose metabolism. While thiazolidinediones enhance glucose uptake in non-cerebral tissues, their impact on brain energy metabolism has not been investigated in vivo. We thus determined whether the thiazolidinedione pioglitazone reverses the decrease in cerebral glucose utilisation (CGU) in a model of brain metabolic deficiency related to Alzheimer's disease. Results are relevant to diabetes because millions of diabetic patients take pioglitazone as an insulin-sensitising drug, and diabetes increases the risk of developing Alzheimer's disease. Materials and methods The regional pattern of CGU was measured with the 2-deoxy [ 14 C] glucose autoradiographic technique in adult awake mice overexpressing transforming growth factor β1 (TGFβ1), and in wild-type littermates. Mice were treated with pioglitazone for 2 months.Results Measurement of CGU in 27 brain regions confirmed that TGFβ1 overexpression induced hypometabolism across the brain. Pioglitazone did not reverse the effect of TGFβ1 overexpression and decreased regional CGU in control animals by up to 23%. The extent of the regional CGU decrease induced by pioglitazone, but not that induced by TGFβ1, correlated strongly with basal CGU, suggesting that the higher the local metabolic rate the greater the reduction of CGU effected by pioglitazone. Conclusions/interpretation In contrast to its stimulatory effect in non-cerebral tissues, chronic treatment with pioglitazone decreases CGU in vivo. This evidence does not support the hypothesis that pioglitazone could act as a metabolic enhancer in Alzheimer's disease, and raises the question of how thiazolidinediones could be beneficial in neurodegenerative diseases.

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Section: Discussionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Pioglitazone does not increase cerebral glucose utilisation in a murine model of Alzheimer’s disease and decreases it in wild-type mice

2006

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“…Troglitazone treatment of L6 myocytes (15) and isolated rat cardiac myocytes (16) increased glucose transport and the expression of both GLUT1 and GLUT4. This effect was independent of differentiation because it occurred even in L6 cells that were not differentiated into myotubes (15) or in BC3H-1 myocytes (with pioglitazone) (17) that are incapable of differentiation. It should be noted that the non-differentiated myocytes express only GLUT1 and it is this isoform that is upregulated by thiazolidinedione treatment.…”

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confidence: 98%

Thiazolidinediones and their effects on glucose transporters

Ciaraldi

Henry²

1997

European Journal of Endocrinology

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“…In many studies, TZDs were found to stimulate glucose transport into skeletal muscle in vitro [16,70,111,112,113,114,115,116,117,118,119,120] but the accompanying changes in intracellular glucose fluxes were rather inconsistent, ranging from stimulation to inhibition of both glucose oxidation and glycogen synthesis [16,70,111,112,113,114,121]. The heterogeneity of effects on intracellular glucose routing is obviously related to the diversity in experimental settings.…”

Section: Skeletal Musclementioning

confidence: 99%

“…The heterogeneity of effects on intracellular glucose routing is obviously related to the diversity in experimental settings. Studies varied with regard to the structure and concentration of the TZD used, the period of exposure, and the muscle preparations which included perfused rat hindlimb [120], freshly isolated rat soleus muscle [16,111,112,113,121], pre-cultured human muscle biopsies [114,115,116], and permanently cultured muscle cell lines [70,117,118,119]. Comparing different studies is further complicated by the lipophilic character of TZDs that strongly bind to protein [122], which implies a modulation of the bioavailable TZD concentration in vitro by the quantity and quality of protein and detergent added to the incubation or perfusion medium.…”

Section: Skeletal Musclementioning

confidence: 99%

Thiazolidinediones: metabolic actions in vitro

Fürnsinn¹,

Waldhäusl

2002

Diabetologia

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To unravel the molecular mechanisms and the causal chain of how thiazolidinediones (TZDs) affect glucose homeostasis, it is helpful to analyse their direct influence on isolated specimens of fat, muscle, and liver in vitro. Studies on isolated adipocytes have shown that the nuclear peroxisome proliferator-activated receptor-γ (PPARγ) is an important molecular target for TZDs, through which they trigger adipocyte differentiation and adipose tissue remodelling. It is not clear, however, if the activation of PPARγ in adipose tissue is the cause of all the metabolic actions of TZDs. Based on in vitro studies, two hypotheses have been developed. The first emphasizes PPARγ-mediated actions on adipose tissue, suggesting that insulin sensitization of skeletal muscle and liver is triggered indirectly by changes in circulating concentrations of adipocyte-derived non-esterified fatty acids and peptide hormones. The second states that TZDs improve glucose homeostasis independently from adipose tissue actions by the direct interaction with muscle and liver. This hypothesis is supported by direct TZD actions on fuel metabolism of skeletal muscle and liver in vitro, which seem to be independent from PPARγ signalling. Major progress has been made in understanding the mechanisms involved in the effects of TZDs on adipose tissue but the causal chain responsible for their antihyperglycaemic action is still not clear. The involvement of other molecular targets in addition to PPARγ, of adipocyte-derived messengers, and of direct interaction with skeletal muscle and liver have yet to be clarified. [Diabetologia (2002[Diabetologia ( ) 45:1211[Diabetologia ( -1223

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Regulation of glucose transport by pioglitazone in cultured muscle cells

Cited by 49 publications

References 46 publications

Pioglitazone does not increase cerebral glucose utilisation in a murine model of Alzheimer’s disease and decreases it in wild-type mice

Pioglitazone does not increase cerebral glucose utilisation in a murine model of Alzheimer’s disease and decreases it in wild-type mice

Thiazolidinediones and their effects on glucose transporters

Thiazolidinediones: metabolic actions in vitro

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