In VivoEffects of Pioglitazone on Uncoupling Protein-2 and -3 mRNA Levels in Skeletal Muscle of Hyperglycemic KK Mice

Shimokawa, Teruhiko; Kato, Miyuki; Watanabe, Yuka; Hirayama, Reiko; Kurosaki, Eiji; Shikama, Hisataka; Hashimoto, Seiichi

doi:10.1006/bbrc.1998.9479

Cited by 37 publications

(21 citation statements)

References 33 publications

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“…10,15,16,23,24 The mechanism by which PPAR ligands up-regulate UCP gene expression is complex. PPAR is a member of the nuclear receptor superfamily that includes receptors for the steroid, thyroid and retinoid hormones.…”

Section: Discussionmentioning

confidence: 99%

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Transcriptional regulation of uncoupling protein-2 gene expression in L6 myotubes

Hatakeyama

Scarpace

2001

Int J Obes

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OBJECTIVE:To increase the understanding of the transcriptional regulation of UCP2 gene expression in skeletal muscle cells, we examined the effect of all-trans-retinoic acid (tRA), a ligand (after the conversion to 9-cis-RA) of the retinoid X receptor (RXR), and linolenic acid, a polyunsaturated fatty acid and peroxisome proliferator-activated receptors (PPARs) ligand, on the expression of UCP2 mRNA in cultured L 6 myotubes. RESEARCH METHODS AND PROCEDURES: UCP2 gene expression in L 6 myotubes was confirmed by Northern blot analysis. The time-and concentration-dependency of tRA and linolenic acid on UCP2 gene expression was assessed by dot blot quantification. The mRNA levels of PPAR subtypes (a, g and d) were determined by RT-PCR. RESULTS: tRA induced UCP2 gene expression in a time-and concentration-dependent manner. Similar to tRA, UCP2 mRNA was markedly increased by 0.5 mM linolenic acid. In L 6 myotubes, PPARd mRNA was abundant, whereas PPARa mRNA was lower and PPARg mRNA was minimal. CONCLUSIONS: UCP2 mRNA expression in L 6 myotubes is up-regulated by tRA and linolenic acid, possibly through a mechanism involving PPAR and RXRs.

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Section: Discussionmentioning

confidence: 99%

“…Shimokawa et al 16 have reported that the PPARg ligand pioglitazone induced an in vivo stimulation of UCP2 mRNA expression in skeletal muscle, especially soleus muscle. In contrast, UCP3 mRNA level is decreased by this ligand, indicating differential in vivo gene regulation.…”

Section: Introductionmentioning

confidence: 99%

Transcriptional regulation of uncoupling protein-2 gene expression in L6 myotubes

Hatakeyama

Scarpace

2001

Int J Obes

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“…In addition, an up-regulation of skeletal muscle UCP3 mRNA was measured in immobilized rats under conditions where glucose uptake was increased (M. Marzolo, D. Ricquier, X. Bigard and B. Serrurier, unpublished work). Studies based on the use of anti-diabetic compounds such as thiazolidinediones also support a role for muscle UCPs in glucose utilization [172,230,248]. Interestingly, Hjeltnes et al [249] measured an increased level of UCP2 and UCP3 mRNAs in skeletal muscle from tetraplegic subjects, and a normalization after electrically stimulated leg cycling under conditions where insulinstimulated glucose uptake was increased.…”

Section: Ucps and Glucose Utilization : A Role In Insulin Resistance ?mentioning

confidence: 97%

“…Interestingly, Hjeltnes et al [249] measured an increased level of UCP2 and UCP3 mRNAs in skeletal muscle from tetraplegic subjects, and a normalization after electrically stimulated leg cycling under conditions where insulinstimulated glucose uptake was increased. Shimokawa et al [248] demonstrated that the UCP3 mRNA level in skeletal muscle was correlated strongly with levels of circulating glucose in rats treated with a thiazolidinedione, suggesting that the thiazolidinediones increased glucose catabolism by up-regulating UCP2 expression.…”

Section: Ucps and Glucose Utilization : A Role In Insulin Resistance ?mentioning

confidence: 99%

The uncoupling protein homologues: UCP1, UCP2, UCP3, StUCP and AtUCP

Ricquier¹,

Bouillaud

2000

Biochemical Journal

614

115

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Animal and plant uncoupling protein (UCP) homologues form a subfamily of mitochondrial carriers that are evolutionarily related and possibly derived from a proton\anion transporter ancestor. The brown adipose tissue (BAT) UCP1 has a marked and strongly regulated uncoupling activity, essential to the maintenance of body temperature in small mammals. UCP homologues identified in plants are induced in a cold environment and may be involved in resistance to chilling. The biochemical activities and biological functions of the recently identified mammalian UCP2 and UCP3 are not well known. However, recent data support a role for these UCPs in State 4 respiration, respiration uncoupling and proton leaks in mitochondria. Moreover, genetic studies suggest that UCP2 and UCP3 play a part in

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“…Long-term exposure to fatty acids uncouples the mitochondrial potential in association with increased expression of UCP-2 in ␤-cells (19). In addition, TZDs upregulate UCP-2 expression in skeletal muscle and white and brown adipose tissue (46,47). These results led us to examine whether PPAR-␥ plays a role in insulin secretion through modifications of lipid metabolism and energy dissipation in ␤-cells.…”

Section: Role Of Ppar-␥ In Adipocyte Differentiation and As A Thriftymentioning

confidence: 99%

Genetic Manipulations of Fatty Acid Metabolism in β-Cells Are Associated With Dysregulated Insulin Secretion

et al. 2002

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Triacylglyceride (TG) accumulation in pancreatic ␤-cells is associated with impaired insulin secretion, which is called lipotoxicity. To gain a better understanding of the pathophysiology of lipotoxicity, we generated three models of dysregulated fatty acid metabolism in ␤-cells. The overexpression of sterol regulatory element binding protein-1c induced lipogenic genes and TG accumulation. Under these conditions, we observed a decrease in glucose oxidation and upregulation of uncoupling protein-2, which might be causally related to the decreased glucose-stimulated insulin secretion. The overexpression of AMP-activated protein kinase was accompanied by decreased lipogenesis, increased fatty acid oxidation, and decreased glucose oxidation; insulin secretions to glucose and depolarization stimuli were decreased, probably because of the decrease in glucose oxidation and cellular insulin content. It was notable that the secretory response to palmitate was blunted, which would suggest a role of the fatty acid synthesis pathway, but not its oxidative pathway in palmitate-stimulated insulin secretion. Finally, we studied islets of PPAR-␥ ؉/؊ mice that had increased insulin sensitivity and low TG content in white adipose tissue, skeletal muscle, and liver. On a high-fat diet, glucose-stimulated insulin secretion was decreased in association with increased TG content in the islets, which might be mediated through the elevated serum free fatty acid levels and their passive transport into ␤-cells. These results revealed some aspects about the mechanisms by which alterations of fatty acid metabolism affect ␤-cell functions. Diabetes 51 (Suppl. 3): S414 -S420, 2002

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In VivoEffects of Pioglitazone on Uncoupling Protein-2 and -3 mRNA Levels in Skeletal Muscle of Hyperglycemic KK Mice

Cited by 37 publications

References 33 publications

Transcriptional regulation of uncoupling protein-2 gene expression in L6 myotubes

Transcriptional regulation of uncoupling protein-2 gene expression in L6 myotubes

The uncoupling protein homologues: UCP1, UCP2, UCP3, StUCP and AtUCP

Genetic Manipulations of Fatty Acid Metabolism in β-Cells Are Associated With Dysregulated Insulin Secretion

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