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

Abstract

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 ...

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

“…The hypothesis that fetal kidney expression of calcium-transporting proteins is permanently programmed by prevailing in-utero glucose and/or calcium concentrations should be tested in future experiments. Such experiments also need to examine related endocrine changes: in a separate study we have found that concentrations of serum parathyroid hormone (PTH) are reduced in 8-week-old OD rats relative to those in OC rats [30].…”

Parental Diabetes: The Akita Mouse as a Model of the Effects of Maternal and Paternal Hyperglycemia in Wildtype Offspring

“…Changes in skeletal development in offspring as a result of maternal high-fat diet [25] and in offspring of rats with streptozotocin induced diabetes [21] have been described previously. The skeletal changes we observed could stem from parental transmission of programming effects, or be the result of the metabolic abnormalities in the offspring.…”

“…In some models a strong metabolic phenotype with the development of obesity can be observed, in other models the metabolic impairment is more subtle, affecting, for example, lipid metabolism. Besides metabolic impairments [15] [17], changes of skeletal development [16], of kidney function [21], of cardiac/vascular function [18], of aortic gene expression [20], of gene expression changes in hypothalamic centers [22], changes in pancreatic beta cells [23] and changes in behavior have been described as results of either diabetic or dysmetabolic mothers. More recently there have been reports on paternal transmission of such effects as well [16] [9].…”

LDL-Related Intolerance to Glucose, Diastolic Hypertension and Additive Effects of Smoking Were Found with Three Female Study Groups

“…Hematuria indicated thin basement membranes during alcohol-related dyslipidemia so that long cessation periods were needed without alcohol consumption, without sugar alcohol, saturated fat and transformed phospholipids. Women with albuminuria had to perceive that about 40% of excreted albumin is degraded during glomerular transcytosis and cannot be detected [60] [68] [69]. Urinary albumin cannot be reabsorbed and can trigger tubular fibrosis with disturbed tubular re-adsorption [60].…”