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Insulin inhibits dexamethasone effect on angiotensinogen gene expression and induction of hypertrophy in rat kidney proximal tubular cells in high glucose.
Endocrinology. 2002 Dec; 143(12):4627-35.E

Abstract

The present studies investigated whether insulin inhibits the stimulatory effect of dexamethasone (DEX) on angiotensinogen (ANG) gene expression and induction of hypertrophy in rat immortalized renal proximal tubular cells (IRPTCs) in a high-glucose milieu. Rat IRPTCs were cultured in monolayer. ANG and ANG mRNA expression in IRPTCs were quantified by a specific RIA for rat ANG and by RT-PCR assay, respectively. A fusion gene containing the full length of the 5'-flanking region of the rat ANG gene linked to a chloramphenicol acetyl transferase reporter gene was introduced into IRPTCs. The level of fusion gene expression was determined by cellular chloramphenicol acetyl transferase enzymatic activity. Cellular hypertrophy was assessed by flow cytometry, cellular p27(Kip1) protein expression, and protein assay. Our results showed that high glucose (i.e. 25 mM) and DEX (10(-7) M) additively stimulated ANG gene expression and induced IRPTC hypertrophy. Insulin inhibited the effect of high glucose and DEX on these parameters. The inhibitory effect of insulin was reversed by PD 98059 (a MAPK inhibitor) but not by wortmannin (a phosphatidylinositol-3-kinase inhibitor). These results demonstrate that insulin is effective in blocking the stimulatory action of high glucose and DEX on ANG gene expression and induction of IRPTC hypertrophy, suggesting its important role in preventing local intrarenal renin-angiotensin system activation and renal proximal tubular cell hypertrophy induced by hyperglycemia and glucocorticoids in vivo.

Authors+Show Affiliations

Université de Montréal, Centre Hospitalier de l'Université de Montréal, Hôtel-Dieu Hospital, Research Center, Montréal, Québec H2W 1T8 Canada.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

12446590

Citation

Zhang, Shao-Ling, et al. "Insulin Inhibits Dexamethasone Effect On Angiotensinogen Gene Expression and Induction of Hypertrophy in Rat Kidney Proximal Tubular Cells in High Glucose." Endocrinology, vol. 143, no. 12, 2002, pp. 4627-35.
Zhang SL, Chen X, Wei CC, et al. Insulin inhibits dexamethasone effect on angiotensinogen gene expression and induction of hypertrophy in rat kidney proximal tubular cells in high glucose. Endocrinology. 2002;143(12):4627-35.
Zhang, S. L., Chen, X., Wei, C. C., Filep, J. G., Tang, S. S., Ingelfinger, J. R., & Chan, J. S. (2002). Insulin inhibits dexamethasone effect on angiotensinogen gene expression and induction of hypertrophy in rat kidney proximal tubular cells in high glucose. Endocrinology, 143(12), 4627-35.
Zhang SL, et al. Insulin Inhibits Dexamethasone Effect On Angiotensinogen Gene Expression and Induction of Hypertrophy in Rat Kidney Proximal Tubular Cells in High Glucose. Endocrinology. 2002;143(12):4627-35. PubMed PMID: 12446590.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Insulin inhibits dexamethasone effect on angiotensinogen gene expression and induction of hypertrophy in rat kidney proximal tubular cells in high glucose. AU - Zhang,Shao-Ling, AU - Chen,Xing, AU - Wei,Chih-Chang, AU - Filep,Janos G, AU - Tang,Shiow-Shih, AU - Ingelfinger,Julie R, AU - Chan,John S D, PY - 2002/11/26/pubmed PY - 2002/12/27/medline PY - 2002/11/26/entrez SP - 4627 EP - 35 JF - Endocrinology JO - Endocrinology VL - 143 IS - 12 N2 - The present studies investigated whether insulin inhibits the stimulatory effect of dexamethasone (DEX) on angiotensinogen (ANG) gene expression and induction of hypertrophy in rat immortalized renal proximal tubular cells (IRPTCs) in a high-glucose milieu. Rat IRPTCs were cultured in monolayer. ANG and ANG mRNA expression in IRPTCs were quantified by a specific RIA for rat ANG and by RT-PCR assay, respectively. A fusion gene containing the full length of the 5'-flanking region of the rat ANG gene linked to a chloramphenicol acetyl transferase reporter gene was introduced into IRPTCs. The level of fusion gene expression was determined by cellular chloramphenicol acetyl transferase enzymatic activity. Cellular hypertrophy was assessed by flow cytometry, cellular p27(Kip1) protein expression, and protein assay. Our results showed that high glucose (i.e. 25 mM) and DEX (10(-7) M) additively stimulated ANG gene expression and induced IRPTC hypertrophy. Insulin inhibited the effect of high glucose and DEX on these parameters. The inhibitory effect of insulin was reversed by PD 98059 (a MAPK inhibitor) but not by wortmannin (a phosphatidylinositol-3-kinase inhibitor). These results demonstrate that insulin is effective in blocking the stimulatory action of high glucose and DEX on ANG gene expression and induction of IRPTC hypertrophy, suggesting its important role in preventing local intrarenal renin-angiotensin system activation and renal proximal tubular cell hypertrophy induced by hyperglycemia and glucocorticoids in vivo. SN - 0013-7227 UR - https://www.unboundmedicine.com/medline/citation/12446590/Insulin_inhibits_dexamethasone_effect_on_angiotensinogen_gene_expression_and_induction_of_hypertrophy_in_rat_kidney_proximal_tubular_cells_in_high_glucose_ L2 - https://academic.oup.com/endo/article-lookup/doi/10.1210/en.2002-220408 DB - PRIME DP - Unbound Medicine ER -