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Functional, molecular, and biochemical characterization of streptozotocin-induced diabetes

Ward, D. T., Yau, S. K., Mee, A. P., Mawer, E. B., Miller, C. A., Garland, H. O. and Riccardi, Daniela 2001. Functional, molecular, and biochemical characterization of streptozotocin-induced diabetes. Journal of the American Society of Nephrology 12 (4) , pp. 779-790.

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Altered divalent cation homeostasis with bone mineral loss, hypercalciuria, and hypomagnesemia have been associated consistently with human diabetes mellitus. This study investigated functional, molecular, and biochemical determinants that accompany this condition in chronically (2 wk) streptozotocin (STZ)-diabetic rats. Catheterized, conscious, diabetic rats on servo-controlled fluid replacement exhibited an increased GFR (+70%) and a substantially raised urinary calcium output (+568%) when compared with control rats. In addition, fractional calcium reabsorption was reduced, indicating that the hypercalciuria was not due solely to an osmotic effect but may involve an actual tubular defect. The expression of proteins involved in renal distal Ca2+ and water transport in STZ-diabetic rats were then studied by Western analysis and immunofluorescence microscopy to investigate the molecular basis of the hypercalciuria. Extracellular Ca2+-sensing receptor abundance was reduced to 52% of control in STZ-diabetes, whereas thiazide-sensitive NaCl cotransporter expression was increased by 192%. Subcutaneous insulin implant rectified both functional and molecular parameters. The levels of calbindin D(28k), plasma membrane Ca2+ ATPase, and aquaporin 1 in whole kidney and of aquaporin 2 in inner medulla were unchanged in diabetic and/or insulin replacement. Blood levels of 1,25(OH)(2)D(3) were reduced in diabetes as were levels of osteocalcin, a marker of bone formation. It is concluded that diabetic hypercalciuria in rats involves elevated GFR with raised urinary output, reduced Ca2+ reabsorption, and impaired bone deposition. Changes in Ca2+-sensing receptor and NaCl cotransporter protein expression could account for the altered divalent cation homeostasis seen during diabetes mellitus.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Publisher: Lippincott, Williams & Wilkins
ISSN: 1046-6673
Last Modified: 04 Jun 2017 08:17

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