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Enarodustat, hypoxia-inducible factor stabilizer, counteracts the diabetic renal energy metabolism alterations in streptozotocin-induced diabetic rats

ABSTRACT: Enarodustat, hypoxia-inducible factor stabilizer, counteracts the diabetic renal energy metabolism alterations in streptozotocin-induced diabetic rats

PROVIDER: PRJNA542935 | ENA |

REPOSITORIES: ENA

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Enarodustat, hypoxia-inducible factor stabilizer, counteracts the diabetic renal energy metabolism alterations in streptozotocin-induced diabetic rats

Project description:We analyzed the effects of enarodustat (JTZ-951; HIF stabilizer) on renal energy metabolism in streptozotocin-induced diabetic rat model. Transcriptome analysis of renal cortex revealed that genes related to fatty acid metabolism and amino acid metabolism were upregulated in diabetes and downregulated by enarodustat, whereas genes related to glucose metabolism were upregulated by enarodustat. Thus, HIF stabilization counteracts the renal energy metabolism alterations occurring in the early stages of diabetic kidney disease.

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Enarodustat, a hypoxia-inducible factor stabilizer, counteracts the diabetic renal energy metabolism alterations in the early stages of diabetic kidney disease

Project description:We analyzed the effects of enarodustat (JTZ-951; HIF stabilizer) on renal energy metabolism in alloxan-induced diabetic mouse model. Transcriptome analysis of renal tissue revealed that genes related to fatty acid metabolism were upregulated in diabetes, whereas genes related to glucose metabolism were upregulated by enarodustat. In addition, genes related to amino acid metabolism were upregulated by diabetes and downregulated by enarodustat. Thus, HIF stabilization counteracts the renal energy metabolism alterations occurring in the early stages of diabetic kidney disease.

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Enarodustat, a hypoxia-inducible factor stabilizer, counteracts the diabetic renal energy metabolism alterations in the early stages of diabetic kidney disease

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Project description:Phloridzin is a dihydrochalcone typically contained in apples. A diet containing 0.5 % phloridzin significantly improves hyperglycemia but not hypoinsulinemia and tissue lipid peroxidation in streptozotocin (STZ)-induced diabetic mice after 14 days. The phloridzin diet has no effect on the alteration of hepatic gene expression in STZ-induced diabetic mice. A quantitative RT-PCR analysis showed a reversal of the STZ induction of the sodium/glucose cotransporter gene Sglt1 and the drug-metabolizing enzyme genes Cyp2b10 and Ephx1 in the small intestine of mice fed a 0.5% phloridzin diet. These mice also showed a reversal of the STZ-mediated renal induction of the glucose-regulated facilitated glucose transporter gene Glut2. Dietary phloridzin improved the abnormal elevations in blood glucose level and the overexpression of Sglt1, Cyp2b10 and Ephx1 in the small intestine of STZ-induced diabetic mice.

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