TY - JOUR
T1 - Increased renal calcium and magnesium transporter abundance in streptozotocin-induced diabetes mellitus
AU - Lee, C. T.
AU - Lien, Y. H.H.
AU - Lai, L. W.
AU - Chen, J. B.
AU - Lin, C. R.
AU - Chen, H. C.
N1 - Funding Information:
This work was supported by a grant from the National Science Council of the Republic of China (NSC94-2314-B-182A-119), and a grant from Dialysis Clinic Inc., a non-profit organization to YHL. Part of this work has been presented at the American Society of Nephrology, 2004, St Louis, MO, USA.
PY - 2006/5
Y1 - 2006/5
N2 - 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.
AB - 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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U2 - 10.1038/sj.ki.5000344
DO - 10.1038/sj.ki.5000344
M3 - Article
C2 - 16557223
AN - SCOPUS:33646711450
SN - 0085-2538
VL - 69
SP - 1786
EP - 1791
JO - Kidney international
JF - Kidney international
IS - 10
ER -