Altered calbindin mRNA expression and calcium regulating hormones in rat diabetic pregnancy

Hamilton, Katherine; Tein, Mark; Glazier, Jocelyn D.; Mawer, E. B.; Berry, J. L.; Balment, R. J.; Boyd, R. D.; Garland, Hugh; Sibley, CP

doi:10.1677/joe.0.1640067

Cited by 19 publications

(10 citation statements)

References 48 publications

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“…Glucose rapidly crosses the placenta down a maternofetal plasma concentration gradient; consequently, and fetuses of diabetic rats show a similar degree of hyperglycaemia as their mothers [28]. If high plasma or tubular glucose inhibits calcium reabsorption in early parts of the nephron, the response in both mother and fetus may be to increase distal tubular PMCA and calbindin-D 28k expression, as we have shown previously in mothers [21]. If such a response in the fetal kidney in utero persisted in the normoglycaemic offspring ex utero, hypocalciuria would develop.…”

Section: Discussionsupporting

confidence: 56%

“…Active transcellular calcium transport in the kidney occurs mainly in the distal portion of the nephron [17] and involves three key proteins: epithelial calcium channel 1 (ECaC1), cal-bindin-D 28K and plasma membrane calcium ATPase (PMCA) [18][19][20]. Altered PMCA [20] and calbindin-D 28K [21] expression has been observed in diabetic rats. No information is available regarding the effect of diabetes on ECaC1 and no data are available on the effects of diabetic pregnancy on the expression of these calcium-transporting proteins in the resulting offspring.…”

Section: Introductionmentioning

confidence: 99%

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Diabetes in rat pregnancy alters renal calcium and magnesium reabsorption and bone formation in adult offspring

et al. 2005

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Aims/hypothesis: We tested the hypothesis that diabetes in pregnancy can result in the in-utero reprogramming of renal calcium and magnesium handling and of bone formation in the offspring, which persists into adulthood. Methods: Male offspring of streptozotocintreated diabetic rats (OD rats) and of control non-diabetic animals (OC rats) were investigated as neonates and at 8, 12 and 16 weeks of age. Results: Compared with OC rats, urinary calcium and magnesium output was significantly reduced in OD rats at every age studied; Na + and K + outputs were unaffected. The renal expression of proteins involved in the tubular reabsorption of calcium (calcium ATPase, calbindin-D 28k and epithelial calcium channel) was increased in OD animals compared with that in OC animals. Additionally, we observed that adult OD rats had lower trabecular and higher cortical femoral bone volumes, explained by deposition of bone on the endosteal surface. Conclusions/interpretation: These data show that diabetes in pregnancy has profound effects on male offspring in terms of renal tubular calcium and magnesium reabsorption and the normal pattern of bone formation. These effects persist into adulthood. Such long-lasting effects of diabetes on kidney and the skeleton were not suspected and could have important implications for the health of children born to diabetic women.

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Section: Discussionsupporting

confidence: 56%

Section: Introductionmentioning

confidence: 99%

Diabetes in rat pregnancy alters renal calcium and magnesium reabsorption and bone formation in adult offspring

et al. 2005

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“…There have been few previous studies that examined renal calbindin-D28k levels in diabetic models using primarily immunoblot methodology [7][8][9]40]. The results in those studies, however, were not conclusive and did not provide information about localization of changes.…”

Section: Discussionmentioning

confidence: 99%

Proteomic Identification and Immunolocalization of Increased Renal Calbindin-D28k Expression in OVE26 Diabetic Mice

Thongboonkerd¹,

Zheng²,

McLeish³

et al. 2005

Rev Diab Stud

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■ AbstractDiabetic nephropathy is a common diabetic complication that is associated with alterations in the expression of several renal proteins and abnormal calcium homeostasis. We performed proteomic analysis to screen for global changes of renal protein expression in diabetic kidney. Proteins extracted from the whole kidney of 120-day-old OVE26 (a transgenic model of Type 1 diabetes) and FVB (non-diabetic background strain) mice were separated by two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) and visualized by SYPRO Ruby staining (n = 5 in each group). Quantitative intensity analysis revealed 41 differentially expressed proteins, of which 30 were identified by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS) followed by peptide mass fingerprinting. One of the altered proteins with the greatest magnitude of change was the calcium-binding protein, calbindin-D28k, whose expression was increased 6.7-fold in diabetic kidney. We confirmed the increase in calbindin-D28k expression in diabetic kidney by Western blot analysis. Immunohistochemical study demonstrated that calbindin-D28k expression was markedly increased in tubular epithelial cells of distal convoluted tubules (DCT), collecting ducts (CD), and proximal convoluted tubules (PCT) in diabetic kidney. Calbindin-D28k plays a critical role in maintaining calcium homeostasis. The elevation in renal calbindin-D28k expression in our model may indicate a compensatory mechanism to overcome hypercalciuria in diabetes.

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“…Serum was collected from a separate group of 8-wk-old rats (OC, n ϭ 7; OD, n ϭ 9). PTH concentrations were measured using a rat PTH immunoradiometric assay kit (Nichols Diagnostics, Cambridge, UK), as described previously (23).…”

Section: Methodsmentioning

confidence: 99%

Increased Renal Tubular Reabsorption of Calcium and Magnesium by the Offspring of Diabetic Rat Pregnancy

et al. 2005

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Diabetic pregnancy has a marked influence on offspring calcium and magnesium homeostasis. Urinary excretion of calcium and magnesium is reduced, yet offspring of diabetic pregnancy exhibit hypomagnesemia and hypocalcemia. The aim of this study was to measure renal hemodynamic and tubular function in the offspring of diabetic (OD) and control, nondiabetic (OC) rats at 4 and 8 wk of age to determine the glomerular and tubular mechanisms through which renal calcium and magnesium handling are programmed in utero. The fraction of filtered calcium that was excreted was significantly lower in OD at both 4 and 8 wk of age [8 wk: OC (n ϭ 6), 11.8 Ϯ 2.9 versus OD (n ϭ 5), 4.3 Ϯ 0.6%; p Ͻ 0.05] and that of magnesium was lower at 8 wk of age [OC (n ϭ 6), 42.4 Ϯ 7.5 versus OD (n ϭ 5), 13.0 Ϯ 1.7%; p Ͻ 0.01]. This increased reabsorption occurred despite an elevated GFR in OD. These findings clearly indicate that tubular reabsorptive mechanisms for calcium and magnesium are increased markedly in OD. Serum PTH concentration was reduced in 8-wk-old OD [OC (n ϭ 7), 539.4 Ϯ 142.1 versus OD (n ϭ 9), 174.3 Ϯ 69.4 pg/ml; p Ͻ 0.05], consistent with previous reports in human infants. Taken together, these observations suggest that the basis for the altered renal magnesium and calcium handling in OD involves increased tubular transport activity and possibly increased sensitivity of these mechanisms to PTH. Diabetic pregnancy has a marked impact on maternal calcium and magnesium homeostasis in both humans and rats. Hypomagnesemia has been widely reported in human diabetic pregnancy (1-3), and diabetic pregnant rats display a marked increase in urinary magnesium excretion (4,5). A reduction in third-trimester plasma calcium concentration has been observed in human diabetic pregnancy in one study (3), but the majority of studies have found no difference in calcium concentrations between normal and diabetic pregnancies. However, in the diabetic rat, pregnancy is associated with marked increases in urinary calcium (4,5) and hypocalcemia in some (4) but not all studies (6).These changes in maternal divalent ion handling have a profound impact on the developing fetus. Human offspring of diabetic pregnancy exhibit hypomagnesemia and hypocalcemia as neonates (2,7-9). In the rat, renal handling of calcium and magnesium is also altered in the offspring of streptozotocin (STZ)-treated diabetic rats (OD). We recently reported that OD retain both calcium and magnesium as neonates and that this continues into adulthood (10). These changes in divalent ion homeostasis also occur in conjunction with changes in bone structure. Human offspring of diabetic pregnancy are susceptible to congenital malformations, including skeletal abnormalities (11), and have lower bone mineral content (12). Reduced bone mineral content and abnormal skeletal development have also been observed in the offspring of STZ-treated diabetic rat mothers (13,14). We recently extended these observations and showed that offspring of STZ-treated diabetic rats have reduced trabecular and ...

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Altered calbindin mRNA expression and calcium regulating hormones in rat diabetic pregnancy

Cited by 19 publications

References 48 publications

Diabetes in rat pregnancy alters renal calcium and magnesium reabsorption and bone formation in adult offspring

Diabetes in rat pregnancy alters renal calcium and magnesium reabsorption and bone formation in adult offspring

Proteomic Identification and Immunolocalization of Increased Renal Calbindin-D28k Expression in OVE26 Diabetic Mice

Increased Renal Tubular Reabsorption of Calcium and Magnesium by the Offspring of Diabetic Rat Pregnancy

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