Troglitazone inhibits expression of the phosphoenolpyruvate carboxykinase gene by an insulin-independent mechanism

Davies, Gerald F.; Khandelwal, Ramji L.; Roesler, William J.

doi:10.1016/s0167-4889(99)00080-4

Cited by 38 publications

(28 citation statements)

References 37 publications

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“…So, the observed upregulation of these two genes could very well be a secondary effect of decreased insulin. In contrast to this, GAPDH mRNA expression is induced by insulin in rat hepatoma cells (Davies et al 1999), so the observed upregulation of this gene cannot be ascribed to the changes in circulating insulin levels.…”

Section: Discussionmentioning

confidence: 72%

“…In rat hepatoma cells, insulin has previously been shown to decrease the half-life of glycogen synthase mRNA (Okubo et al 1991), and the mRNA expression of glucose-6-phosphatase is also strongly decreased by insulin in primary rat hepatocytes (Davies et al, 1999). So, the observed upregulation of these two genes could very well be a secondary effect of decreased insulin.…”

Section: Discussionmentioning

confidence: 95%

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Identification of hepatic transcriptional changes in insulin-resistant rats treated with peroxisome proliferator activated receptor-alpha agonists

Frederiksen¹,

Wulf²,

Wassermann³

et al. 2003

Journal of Molecular Endocrinology

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Peroxisome proliferator activated receptor (PPAR)-α controls the expression of multiple genes involved in lipid metabolism, and activators of PPAR-α, such as fibrates, are commonly used drugs in the treatment of hypertriglyceridemia and other dyslipidemic states. Recent data have also suggested a role for PPAR-α in insulin resistance and glucose homeostasis. In the present study, we have assessed the transcriptional and physiological responses to PPAR-α activation in a diet-induced rat model of insulin resistance. The two PPAR-α activators, fenofibrate and Wy-14643, were dosed at different concentrations in high-fat fed Sprague-Dawley rats, and the transcriptional responses were examined in liver using cDNA microarrays. In these analyses, 98 genes were identified as being regulated by both compounds. From this pool of genes, 27 correlated to the observed effect on plasma insulin, including PPAR-α itself and the leukocyte antigen-related protein tyrosine phosphatase (PTP-LAR). PTP-LAR was downregulated by both compounds, and showed upregulation as a result of the high-fat feeding. This regulation was also observed at the protein level. Furthermore, downregulation of PTP-LAR by fenofibric acid was demonstrated in rat FaO hepatoma cells in vitro, indicating that the observed regulation of PTP-LAR by fenofibrate and Wy-14643 in vivo is mediated as a direct effect of the PPAR agonists on the hepatocytes. PTP-LAR is one of the first genes involved in insulin receptor signaling to be shown to be regulated by PPAR-α agonists. These data suggest that factors apart from skeletal muscle lipid supply may influence PPAR-α-mediated amelioration of insulin resistance.

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Section: Discussionmentioning

confidence: 72%

Section: Discussionmentioning

confidence: 95%

Identification of hepatic transcriptional changes in insulin-resistant rats treated with peroxisome proliferator activated receptor-alpha agonists

Frederiksen¹,

Wulf²,

Wassermann³

et al. 2003

Journal of Molecular Endocrinology

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“…Our data in zebrafish is similar to that seen in mammalian tissue culture. For example, sulfonylurea and metformin exposure reduce PEPCK expression in liver cell lines and rat hepatocytes respectively (Davies et al 1999, Yuan et al 2002. Rosiglitazone can directly affect PEPCK expression, via PPAR elements in the promoter region (Duplus et al 2003).…”

Section: Discussionmentioning

confidence: 99%

Larval zebrafish as a model for glucose metabolism: expression of phosphoenolpyruvate carboxykinase as a marker for exposure to anti-diabetic compounds

Elo¹,

Villano²,

Govorko³

et al. 2007

Journal of Molecular Endocrinology

141

121

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The zebrafish model system is one of the most widely used animal models for developmental research and it is now becoming an attractive model for drug discovery and toxicological screening. The completion of sequencing the zebrafish genome and the availability of full-length cDNAs and DNA microarrays for expression analysis, in addition to techniques for generating transgenic lines and targeted mutations, have made the zebrafish model even more attractive to researchers. Recent data indicate that the regulation of glucose metabolism in zebrafish, through the production of insulin, is similar to mammalian models, and many of the genes involved in regulating blood glucose levels have been identified in zebrafish. The data presented here show that adult zebrafish respond to anti-diabetic drugs similarly to mammalian models, by reducing blood glucose levels. Furthermore, we show that the expression of phosphoenolpyruvate carboxykinase (PEPCK), which catalyzes a rate-limiting step in gluconeogenesis and is transcriptionally regulated by glucagon and insulin, is regulated in larval zebrafish similarly to that seen in mammalian systems, and changes in PEPCK expression can be obtained through real-time PCR analysis of whole larval RNA. Taken together, these data suggest that larval zebrafish may be an appropriate model for the examination of glucose metabolism, using PEPCK as an indicator of blood glucose levels.

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“…22) Thus the derivatives improve signal transduction downstream of IRS-1 and the effect of insulin increase in target organs. 23) Troglitazone was reported to suppress mRNA expressions of G6Pase and PEPCK 24) and induce expression of GLUT4 in adipose cells. 25) mRNA expression of AQP3 in Caco-2 cells was found to decrease by treatment with troglitazone in this study.…”

Section: Discussionmentioning

confidence: 99%

Regulators for Blood Glucose Level Affect Gene Expression of Aquaporin 3

Higuchi

Kubota

Iguchi

et al. 2006

Biological & Pharmaceutical Bulletin

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Preston and Agre 1) first cloned the water channel protein named as an aquaporin (AQP) in the membrane of erythrocytes in 1991. Thirteen molecular species of AQPs, AQP0-12, have been identified to date. These AQPs were classified into two groups, AQP0, 1, 2, 4, 5, 6, and 8 and AQP3, 7, 9, 10, 11, and 12, the former group selectively permeabilizing water only and the latter, named as aquaglyceroporins, permeabilizing not only water, but also water-soluble low-molecular weight molecules such as glycerol and urea. Although AQPs are widely distributed in almost all human tissues, they show specific tissue localization.2) AQP1,3,4,7,8,10, and 11 were reported to be expressed in the gastrointestinal tract and seem to play a role in absorption of water.3) However, it is still unclear what substances other than water are permeabilized by these AQPs in these sites.AQP3 has been observed expressed in human ileum, colon, jejunum, liver, and pancreas and highly expressed on basal membrane of epithelial cells in ileum and colon. 4) From observations in AQP3-deficient mice, AQP3 was speculated related to renal failure caused by nephrogenic diabetes insipidus and hydronephrosis, absorption of glycerol from decreases of glycerol levels in serum, skin hydration from promotion of dry skin, and occurrence of diarrhea and constipation.2,5) Although lethal dysfunctions caused by deficiency of AQP3 in mice have not been reported so far, AQP3 seems to be required to maintain healthy living. Itoh et al. 6) found that AQP3 expression was increased by treatment with vasoactive intestinal polypeptide (VIP) in human colonic epithelial cells and suggested that increased expression of AQP3 by VIP caused exacerbation of diarrhea because VIP was closely linked to diarrhea onset through controlling gastrointestinal peristaltic motion and secretion of water and electrolytes.The physiological roles related to permeation of low-molecular weight molecules by AQP3 are still unclear in the gastrointestinal tract although the roles on water permeation were studied in depth as described above. mRNA expression of AQP7, a closely related species to AQP3 and classified as an aquaglyceroporin, was reported regulated by insulin in adipose cells. 7) Although the action mechanisms of insulin have been well studied, it has rarely been reported that AQPs are involved in the process of the insulin reaction. The finding of suppression of AQP7 expression by insulin suggests the possibility that insulin controls release of glycerol from adipose cells through AQP7. AQP7 probably contributes to decrease of blood glucose level. Since glycerol is involved in digested nutrients and AQP3 is able to permeabilize glycerol, as dose AQP7, it seems appropriate to consider that AQP3 is responsible for absorption of glycerol in digestive organs. Therefore we first examined whether AQP3 expression was affected by insulin and found that mRNA expression of AQP3 was decreased by treatment with insulin. Herein, we investigate how hormones including insulin and antidiabetic agents ...

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Troglitazone inhibits expression of the phosphoenolpyruvate carboxykinase gene by an insulin-independent mechanism

Cited by 38 publications

References 37 publications

Identification of hepatic transcriptional changes in insulin-resistant rats treated with peroxisome proliferator activated receptor-alpha agonists

Identification of hepatic transcriptional changes in insulin-resistant rats treated with peroxisome proliferator activated receptor-alpha agonists

Larval zebrafish as a model for glucose metabolism: expression of phosphoenolpyruvate carboxykinase as a marker for exposure to anti-diabetic compounds

Regulators for Blood Glucose Level Affect Gene Expression of Aquaporin 3

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