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Research ArticleGASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

Reduced Expression of Organic Cation Transporters rOCT1 and rOCT2 in Experimental Diabetes

Brett Grover, Donna Buckley, Arthur R. Buckley and William Cacini
Journal of Pharmacology and Experimental Therapeutics March 2004, 308 (3) 949-956; DOI: https://doi.org/10.1124/jpet.103.058388
Brett Grover
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Donna Buckley
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Arthur R. Buckley
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William Cacini
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Abstract

Recent reports have documented a functional deficit of organic cation transport in diabetic rats by an unknown mechanism. This study was designed to test the hypothesis that experimental diabetes decreases expression of organic cation transporters at the basolateral membrane. Streptozotocin-induced diabetic rats were maintained for varying durations after induction of diabetes. A second group of age-matched control rats was maintained in a parallel manner. Kinetic analysis of tetraethylammonium accumulation in freshly isolated proximal tubular cells indicated a significantly lower Vmax value for the diabetics versus controls with no statistical difference in Km values between the two groups. Cortex sections were processed by standard procedures for Northern and immunoblot analysis. Protein expression of the organic cation transporters rOCT1 and rOCT2 progressively decreased with increasing duration of diabetes. After 21 days of diabetes, rOCT1 and rOCT2 were maximally reduced by 50 and 70%, respectively. Quantification of mRNA expression revealed that the roct1 transcript remained unchanged, whereas the roct2 transcript was decreased by 50% after 14 days of diabetes. Treatment with insulin prevented the reductions in transporter levels. These results support the hypothesis by demonstrating that experimental diabetes decreased expression of both rOCT1 and rOCT2 protein and also of roct2 mRNA accumulation. On the other hand, roct1 mRNA levels were unaffected by the diabetic state. This suggests that differences in rOCT2 protein may result from transcriptional and/or translational changes, whereas rOCT1 deficits may be due to posttranscriptional alterations.

Footnotes

  • DOI: 10.1124/jpet.103.058388.

  • ABBREVIATIONS: STZ, streptozotocin; OCT, organic cation transporter; BLM, basolateral membrane; TEA, tetraethylammonium; γGT, γ-glutamyltranspeptidase; BSA, bovine serum albumin.

    • Received August 18, 2003.
    • Accepted November 25, 2003.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 308 (3)
Journal of Pharmacology and Experimental Therapeutics
Vol. 308, Issue 3
1 Mar 2004
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Research ArticleGASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

Reduced Expression of Organic Cation Transporters rOCT1 and rOCT2 in Experimental Diabetes

Brett Grover, Donna Buckley, Arthur R. Buckley and William Cacini
Journal of Pharmacology and Experimental Therapeutics March 1, 2004, 308 (3) 949-956; DOI: https://doi.org/10.1124/jpet.103.058388

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Research ArticleGASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

Reduced Expression of Organic Cation Transporters rOCT1 and rOCT2 in Experimental Diabetes

Brett Grover, Donna Buckley, Arthur R. Buckley and William Cacini
Journal of Pharmacology and Experimental Therapeutics March 1, 2004, 308 (3) 949-956; DOI: https://doi.org/10.1124/jpet.103.058388
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