Increased renal calcium and magnesium transporter abundance in streptozotocin-induced diabetes mellitus

C. T. Lee, Y. H H Lien, Li-Wen Lai, J. B. Chen, C. R. Lin, H. C. Chen

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Diabetes is associated with renal calcium and magnesium wasting, but the molecular mechanisms of these defects are unknown. We measured renal calcium and magnesium handling and investigated the effects of diabetes on calcium and magnesium transporters in the thick ascending limb and distal convoluted tubule in streptozotocin (STZ)-induced diabetic rats. Rats were killed 2 weeks after inducing diabetes, gene expression of calcium and magnesium transporters in the kidney was determined by real-time polymerase chain reaction, and the abundance of protein was assessed by immunoblotting. Our results showed that diabetic rats had significant increase in the fractional excretion for calcium and magnesium (both P < 0.01), but not for sodium. Reverse transcriptase-polymerase chain reaction revealed significant increases in messenger RNA abundance of transient potential receptor (TRP) V5 (223 ± 10%), TRPV6 (177 ± 9%), calbindin-D28k (231 ± 8%), and TRPM6 (165 ± 8%) in diabetic rats. Sodium chloride cotransporter was also increased (207 ± 10%). No change was found in paracellin-1 (cortex: 108 ± 8%; medulla: 110 ± 10%). Immunofluorescent studies of renal sections showed significant increase in calbindin-D28k (238 ± 10%) and TRPV5 (211 ± 10%), but no changes in paracellin-1 in Western blotting (cortex: 110 ± 7%; medulla: 99 ± 7%). Insulin administration completely corrected the hyperglycemia-associated hypercalciuria and hypermagnesiuria, and reversed the increase of calcium and magnesium transporter abundance. In conclusion, our results demonstrated increased renal calcium and magnesium transporter abundance in STZ-induced diabetic rats, which may represent a compensatory adaptation for the increased load of calcium and magnesium to the distal tubule.

Original languageEnglish (US)
Pages (from-to)1786-1791
Number of pages6
JournalKidney International
Volume69
Issue number10
DOIs
StatePublished - May 2006

Fingerprint

Experimental Diabetes Mellitus
Magnesium
Diabetes Mellitus
Calcium
Kidney
Calbindin 1
Streptozocin
Sodium Chloride Symporters
Hypercalciuria
Reverse Transcriptase Polymerase Chain Reaction
Immunoblotting
Hyperglycemia
Real-Time Polymerase Chain Reaction
Extremities
Western Blotting
Sodium
Insulin
Gene Expression
Messenger RNA

Keywords

  • Diabetes mellitus
  • Hypercalciuria
  • Hypermagnesiuria
  • Paracellin-1
  • TRPM6
  • TRPV5

ASJC Scopus subject areas

  • Nephrology

Cite this

Increased renal calcium and magnesium transporter abundance in streptozotocin-induced diabetes mellitus. / Lee, C. T.; Lien, Y. H H; Lai, Li-Wen; Chen, J. B.; Lin, C. R.; Chen, H. C.

In: Kidney International, Vol. 69, No. 10, 05.2006, p. 1786-1791.

Research output: Contribution to journalArticle

Lee, C. T. ; Lien, Y. H H ; Lai, Li-Wen ; Chen, J. B. ; Lin, C. R. ; Chen, H. C. / Increased renal calcium and magnesium transporter abundance in streptozotocin-induced diabetes mellitus. In: Kidney International. 2006 ; Vol. 69, No. 10. pp. 1786-1791.
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abstract = "Diabetes is associated with renal calcium and magnesium wasting, but the molecular mechanisms of these defects are unknown. We measured renal calcium and magnesium handling and investigated the effects of diabetes on calcium and magnesium transporters in the thick ascending limb and distal convoluted tubule in streptozotocin (STZ)-induced diabetic rats. Rats were killed 2 weeks after inducing diabetes, gene expression of calcium and magnesium transporters in the kidney was determined by real-time polymerase chain reaction, and the abundance of protein was assessed by immunoblotting. Our results showed that diabetic rats had significant increase in the fractional excretion for calcium and magnesium (both P < 0.01), but not for sodium. Reverse transcriptase-polymerase chain reaction revealed significant increases in messenger RNA abundance of transient potential receptor (TRP) V5 (223 ± 10{\%}), TRPV6 (177 ± 9{\%}), calbindin-D28k (231 ± 8{\%}), and TRPM6 (165 ± 8{\%}) in diabetic rats. Sodium chloride cotransporter was also increased (207 ± 10{\%}). No change was found in paracellin-1 (cortex: 108 ± 8{\%}; medulla: 110 ± 10{\%}). Immunofluorescent studies of renal sections showed significant increase in calbindin-D28k (238 ± 10{\%}) and TRPV5 (211 ± 10{\%}), but no changes in paracellin-1 in Western blotting (cortex: 110 ± 7{\%}; medulla: 99 ± 7{\%}). Insulin administration completely corrected the hyperglycemia-associated hypercalciuria and hypermagnesiuria, and reversed the increase of calcium and magnesium transporter abundance. In conclusion, our results demonstrated increased renal calcium and magnesium transporter abundance in STZ-induced diabetic rats, which may represent a compensatory adaptation for the increased load of calcium and magnesium to the distal tubule.",
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