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Published in: Diabetologia 7/2005

01-07-2005 | Article

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

Authors: H. Bond, K. Hamilton, R. J. Balment, J. Denton, A. J. Freemont, H. O. Garland, J. D. Glazier, C. P. Sibley

Published in: Diabetologia | Issue 7/2005

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Abstract

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 streptozotocin-treated 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-D28k 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.
Literature
1.
go back to reference Gluckman PD, Hanson MJ (2004) Living with the past: evolution, development, and patterns of disease. Science 305:1733–1736CrossRefPubMed Gluckman PD, Hanson MJ (2004) Living with the past: evolution, development, and patterns of disease. Science 305:1733–1736CrossRefPubMed
2.
go back to reference Barker DJP, Hales CN, Fall CHD, Osmond C, Phipps K, Clark PMS (1993) Type II (non-insulin dependent) diabetes mellitus, hypertension and hyperlipidemia (syndrome X): relation to fetal growth. Diabetologia 36:62–67CrossRefPubMed Barker DJP, Hales CN, Fall CHD, Osmond C, Phipps K, Clark PMS (1993) Type II (non-insulin dependent) diabetes mellitus, hypertension and hyperlipidemia (syndrome X): relation to fetal growth. Diabetologia 36:62–67CrossRefPubMed
3.
go back to reference Aerts L, Van Assche FA (1979) Is gestational diabetes an acquired condition? J Dev Physiol 1:219–225PubMed Aerts L, Van Assche FA (1979) Is gestational diabetes an acquired condition? J Dev Physiol 1:219–225PubMed
4.
go back to reference Hoelmans K, Aerst L, Van Assche FA (1991) Evidence for an insulin resistance in the adult offspring of pregnant streptozotocin-diabetic rats. Diabetologia 34:81–85CrossRefPubMed Hoelmans K, Aerst L, Van Assche FA (1991) Evidence for an insulin resistance in the adult offspring of pregnant streptozotocin-diabetic rats. Diabetologia 34:81–85CrossRefPubMed
5.
go back to reference Tsang RC, Kleinman LI, Sutherland JM, Light IJ (1972) Hypocalcaemia in infants of diabetic mothers. Studies in calcium, phosphorus and magnesium metabolism and parathormone responsiveness. J Pediatr 80:384–395PubMed Tsang RC, Kleinman LI, Sutherland JM, Light IJ (1972) Hypocalcaemia in infants of diabetic mothers. Studies in calcium, phosphorus and magnesium metabolism and parathormone responsiveness. J Pediatr 80:384–395PubMed
6.
go back to reference Mimouni F, Tsang RC, Hertzberg VS, Miodovnik M (1986) Polycythemia, hypomagnesemia and hypocalcemia in infants of diabetic mothers. Am J Dis Child 140:798–800PubMed Mimouni F, Tsang RC, Hertzberg VS, Miodovnik M (1986) Polycythemia, hypomagnesemia and hypocalcemia in infants of diabetic mothers. Am J Dis Child 140:798–800PubMed
7.
go back to reference Mimouni F, Loughhead J, Miodovnik M, Khoury J, Tsang RC (1990) Early neonatal predictors of neonatal hypocalcemia in infants of diabetic mothers: an epidemiologic study. Am J Perinatol 7:203–206PubMed Mimouni F, Loughhead J, Miodovnik M, Khoury J, Tsang RC (1990) Early neonatal predictors of neonatal hypocalcemia in infants of diabetic mothers: an epidemiologic study. Am J Perinatol 7:203–206PubMed
8.
go back to reference Mimouni F, Mimouni CP, Loughead JL, Tsang RC (1991) A case-control study of hypocalemia in high risk neonates: racial, but no seasonal differences. J Am Coll Nutr 10:196–199PubMed Mimouni F, Mimouni CP, Loughead JL, Tsang RC (1991) A case-control study of hypocalemia in high risk neonates: racial, but no seasonal differences. J Am Coll Nutr 10:196–199PubMed
9.
go back to reference Tsang RC, Strub R, Brown DR, Steichen J, Hartman C, Chen IW (1976) Hypomagnesemia in infants of diabetic mothers: perinatal studies. J Pediatr 89:115–119PubMed Tsang RC, Strub R, Brown DR, Steichen J, Hartman C, Chen IW (1976) Hypomagnesemia in infants of diabetic mothers: perinatal studies. J Pediatr 89:115–119PubMed
10.
go back to reference Mimouni F, Steichen JJ, Tsang RC, Hertzberg V, Miodovnik M (1988) Decreased bone mineral content in infants of diabetic mothers. Am J Perinatol 5:339–343PubMed Mimouni F, Steichen JJ, Tsang RC, Hertzberg V, Miodovnik M (1988) Decreased bone mineral content in infants of diabetic mothers. Am J Perinatol 5:339–343PubMed
11.
go back to reference Lapillone A, Guerin S, Braillon P, Claris O, Delmas PD, Salle BL (1997) Diabetes during pregnancy does not alter whole body mineral content in infants. J Clin Endocrinol Metab 82:3993–3997CrossRefPubMed Lapillone A, Guerin S, Braillon P, Claris O, Delmas PD, Salle BL (1997) Diabetes during pregnancy does not alter whole body mineral content in infants. J Clin Endocrinol Metab 82:3993–3997CrossRefPubMed
12.
go back to reference Verhaeghe J, Bouillon R, Lissens W, Visser WJ, Van Assche FA (1988) Diabetes and low Ca-P diet have opposite effects on adult and fetal bone mineral metabolism. Am J Physiol 254:E496–E504PubMed Verhaeghe J, Bouillon R, Lissens W, Visser WJ, Van Assche FA (1988) Diabetes and low Ca-P diet have opposite effects on adult and fetal bone mineral metabolism. Am J Physiol 254:E496–E504PubMed
13.
go back to reference Verhaeghe J, Van Bree R, Van Herck E et al (1999) Pathogenesis of fetal hypomineralization in diabetic rats: evidence for delayed bone maturation. Pediatr Res 45:209–217PubMed Verhaeghe J, Van Bree R, Van Herck E et al (1999) Pathogenesis of fetal hypomineralization in diabetic rats: evidence for delayed bone maturation. Pediatr Res 45:209–217PubMed
14.
go back to reference Mishima N, Sahara N, Shirakawa M, Ozawa H (2002) Effect of streptozotocin-induced diabetes mellitus on alveolar bone deposition in the rat. Arch Oral Biol 47:843–849CrossRefPubMed Mishima N, Sahara N, Shirakawa M, Ozawa H (2002) Effect of streptozotocin-induced diabetes mellitus on alveolar bone deposition in the rat. Arch Oral Biol 47:843–849CrossRefPubMed
15.
go back to reference Braddock R, Siman CM, Hamilton K, Garland HO, Sibley CP (2002) Gamma-linoleic acid and ascorbate improves skeletal ossification in offspring of diabetic rats. Pediatr Res 51:647–652PubMed Braddock R, Siman CM, Hamilton K, Garland HO, Sibley CP (2002) Gamma-linoleic acid and ascorbate improves skeletal ossification in offspring of diabetic rats. Pediatr Res 51:647–652PubMed
16.
go back to reference Birdsey TJ, Husain SM, Garland HO, Sibley CP (1995) The effect of diabetes mellitus on urinary calcium excretion in pregnant rats and their offspring. J Endocrinol 145:11–18PubMed Birdsey TJ, Husain SM, Garland HO, Sibley CP (1995) The effect of diabetes mellitus on urinary calcium excretion in pregnant rats and their offspring. J Endocrinol 145:11–18PubMed
17.
go back to reference Sharegi GR, Stoner LC (1986) Calcium transport across segments of the rabbit distal nephron in vitro. Am J Physiol 235:F367–F375 Sharegi GR, Stoner LC (1986) Calcium transport across segments of the rabbit distal nephron in vitro. Am J Physiol 235:F367–F375
18.
go back to reference Hoenderop JG, van der Kemp AW, Hartog A et al (1999) Molecular identification of the apical calcium channel in 1,25-dihydroxyvitamin D3-responsive epithelia. J Biol Chem 274:8375–8378CrossRefPubMed Hoenderop JG, van der Kemp AW, Hartog A et al (1999) Molecular identification of the apical calcium channel in 1,25-dihydroxyvitamin D3-responsive epithelia. J Biol Chem 274:8375–8378CrossRefPubMed
19.
go back to reference Borke J, Caride A, Verma AK, Penniston JT, Kumar R (1989) Plasma membrane calcium pump and 28-kDa calcium binding protein in cells of rat kidney distal tubules. Am J Physiol 257:F842–F849PubMed Borke J, Caride A, Verma AK, Penniston JT, Kumar R (1989) Plasma membrane calcium pump and 28-kDa calcium binding protein in cells of rat kidney distal tubules. Am J Physiol 257:F842–F849PubMed
20.
go back to reference Lehotsky J, Kaplan P, Murin R, Raeymaekers L (2002) The role of plasma membrane Ca2+ pumps (PMCAs) in pathologies of mammalian cells. Front Biosci 1:d53–d84 Lehotsky J, Kaplan P, Murin R, Raeymaekers L (2002) The role of plasma membrane Ca2+ pumps (PMCAs) in pathologies of mammalian cells. Front Biosci 1:d53–d84
21.
go back to reference Hamilton K, Tein M, Glazier J et al (2000) Altered calbindin mRNA expression and calcium regulating hormones in rat diabetic pregnancy. J Endocrinol 164:67–76CrossRefPubMed Hamilton K, Tein M, Glazier J et al (2000) Altered calbindin mRNA expression and calcium regulating hormones in rat diabetic pregnancy. J Endocrinol 164:67–76CrossRefPubMed
22.
go back to reference Kavlock RJ, Gray JA (1982) Evaluation of renal function in neonatal rats. Biol Neonate 41:279–288PubMed Kavlock RJ, Gray JA (1982) Evaluation of renal function in neonatal rats. Biol Neonate 41:279–288PubMed
23.
go back to reference Parfitt AM, Drezner MK, Glorieux FH (1987) Bone histomorphometry: standardization of nomenclature, symbols, and units. Report of the ASBMR Histomorphometry Nomenclature Committee. J Bone Miner Res 6:595–610 Parfitt AM, Drezner MK, Glorieux FH (1987) Bone histomorphometry: standardization of nomenclature, symbols, and units. Report of the ASBMR Histomorphometry Nomenclature Committee. J Bone Miner Res 6:595–610
24.
go back to reference Verhaeghe J, Bouillon R, Nyomba BL, Lissens W, Van Assche F (1986) Vitamin D and bone mineral homeostasis during pregnancy in the diabetic BB rat. Endocrinology 118:1019–1025PubMed Verhaeghe J, Bouillon R, Nyomba BL, Lissens W, Van Assche F (1986) Vitamin D and bone mineral homeostasis during pregnancy in the diabetic BB rat. Endocrinology 118:1019–1025PubMed
25.
go back to reference Garland HO, Harris PJ, Morgan TO (1991) Calcium transport in the proximal convoluted tubule and loop of Henle of rats made diabetic with streptozotocin. J Endocrinol 131:373–380PubMed Garland HO, Harris PJ, Morgan TO (1991) Calcium transport in the proximal convoluted tubule and loop of Henle of rats made diabetic with streptozotocin. J Endocrinol 131:373–380PubMed
26.
go back to reference Bronner F, Stein WD (1988) CaBP facilitates intracellular diffusion for calcium pumping in distal convoluted tubule. Am J Physiol 255:F558–F562PubMed Bronner F, Stein WD (1988) CaBP facilitates intracellular diffusion for calcium pumping in distal convoluted tubule. Am J Physiol 255:F558–F562PubMed
27.
go back to reference Bond H, Sibley CP, Balment RJ, Ashton N (2003) Altered renal calcium handling by the offspring of diabetic rats. J Physiol 552P:P110 Bond H, Sibley CP, Balment RJ, Ashton N (2003) Altered renal calcium handling by the offspring of diabetic rats. J Physiol 552P:P110
28.
go back to reference Holemans K, Van Bree R, Verhaeghe J, Meurrens K, Van Assche FA (1997) Maternal semistarvation and streptozotocin-diabetes in rats have different effects on the in vivo glucose uptake by peripheral tissues in their female adult offspring. J Nutr 127:1371–1376PubMed Holemans K, Van Bree R, Verhaeghe J, Meurrens K, Van Assche FA (1997) Maternal semistarvation and streptozotocin-diabetes in rats have different effects on the in vivo glucose uptake by peripheral tissues in their female adult offspring. J Nutr 127:1371–1376PubMed
29.
go back to reference Husain SM, Birdsey TJ, Glazier JD, Mughal MZ, Garland HO, Sibley CP (1994) Effect of diabetes mellitus on maternofetal flux of calcium and magnesium and calbindin9K mRNA expression in rat placenta. Pediatr Res 35:376–381PubMed Husain SM, Birdsey TJ, Glazier JD, Mughal MZ, Garland HO, Sibley CP (1994) Effect of diabetes mellitus on maternofetal flux of calcium and magnesium and calbindin9K mRNA expression in rat placenta. Pediatr Res 35:376–381PubMed
30.
go back to reference Bond H, Sibley CP, Balment RJ, Ashton N (2005) Increased renal tubular reabsorption of calcium and magnesium by the offspring of diabetic rat pregnancy. Pediatr Res (in press) Bond H, Sibley CP, Balment RJ, Ashton N (2005) Increased renal tubular reabsorption of calcium and magnesium by the offspring of diabetic rat pregnancy. Pediatr Res (in press)
31.
go back to reference Mughal MZ, Eelloo JA, Roberts S et al (2003) Intrauterine programming of urinary calcium and magnesium excretion in children born to mothers with insulin-dependent diabetes mellitus. Arch Dis Child (in press) Mughal MZ, Eelloo JA, Roberts S et al (2003) Intrauterine programming of urinary calcium and magnesium excretion in children born to mothers with insulin-dependent diabetes mellitus. Arch Dis Child (in press)
Metadata
Title
Diabetes in rat pregnancy alters renal calcium and magnesium reabsorption and bone formation in adult offspring
Authors
H. Bond
K. Hamilton
R. J. Balment
J. Denton
A. J. Freemont
H. O. Garland
J. D. Glazier
C. P. Sibley
Publication date
01-07-2005
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 7/2005
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-005-1804-5

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