Na+-H+ exchange and Na+-dependent transport systems in streptozotocin diabetic rat kidneys

El-Seifi, S.; Freiberg, J. M.; Kinsella, James L.; Liu, Cheng; Sacktor, Bertram

doi:10.1152/ajpregu.1987.252.1.r40

Cited by 17 publications

(18 citation statements)

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“…In order to understand these findings, it is important to discuss the known effects of diabetes mellitus and thyroparathyroidectomy on urinary acidification. In micropuncture and microperfusion experiments it has been demonstrated that proximal tubular Na + reabsorption is increased in diabetes mellitus (30,31) and that the proximal reabsorption rates of bicarbonate are stimulated (1); in the present study, since the urinary flow as well as the final body weight were unchanged, the lower FE Na + seen in DM reflects an increased tubular reabsorption of Na + rather than a decrease in the extracellular volume status. On the other hand, previous studies from this laboratory (32) have shown that the rates of bicarbonate reabsorption in the proximal tubule of TPTX rats were decreased to the same extent as in a model of intact rats, whose tubules were perfused with a solution containing EGTA, an agent that chelates calcium.…”

Section: Discussionsupporting

confidence: 43%

Effect of thyroparathyroidectomy on urinary acidification in diabetic rats

Zaladek-Gil

Cavanal

Gomes

et al. 1999

Braz J Med Biol Res

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In previous studies we have shown stimulation of renal acid excretion in the proximal tubules of rats with diabetes of short duration, with no important alterations in glomerular hemodynamics; on the other hand, in thyroparathyroidectomized rats (TPTX model), a significant decrease in renal acid excretion, glomerular filtration rate (GFR) and renal plasma flow (RPF) was detected. Since important changes in the parathyroid hormone-vitamin D-Ca axis are observed in the diabetic state, the present study was undertaken to investigate the renal repercussions of thyroparathyroidectomy in rats previously made diabetic by streptozotocin (45 mg/kg). Four to 6 days after the induction of diabetes (DM), a group of rats were thyroparathyroidectomized (DM + TPTX). Renal functional parameters were evaluated by measuring the inulin and sodium para-aminohippurate clearance on the tenth day. The decrease in the GFR and RPF observed in TPTX was not reversed by diabetes since the same alterations were observed in DM + TPTX. Net acid (NA) excretion was unchanged in DM (6.19 ± 0.54), decreased in TPTX (3.76 ± 0.25) and returned to normal levels in DM + TPTX (5.54 ± 0.72) when compared to the control group (6.34 ± 0.14 µmol min -1 kg -1 ). The results suggest that PTH plays an important vasodilator role regarding glomerular hemodynamics, since in its absence the impairment in GFR and RPF was not reversed by the diabetic state. However, with respect to acid excretion, the presence of diabetes was able to overcome the negative stimulus represented by TPTX.

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Section: Discussionsupporting

confidence: 43%

Effect of thyroparathyroidectomy on urinary acidification in diabetic rats

Zaladek-Gil

Cavanal

Gomes

et al. 1999

Braz J Med Biol Res

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“…Many abnormalities of the diabetic state have previously been shown to be corrected by insulin therapy (7,8,38,39). It was therefore of interest to examine the effect of this therapy on the enhanced Na+-H+ exchange associated with diabetes.…”

Section: Resultsmentioning

confidence: 99%

“…In this regard, recent studies in renal proximal tubular brush-border membrane vesicles isolated from streptozotocininduced diabetic rats have demonstrated an increase in electroneutral amiloride-sensitive, Na'-H' exchange activity in these preparations compared to their control counterparts, which was partially corrected by insulin administration (7,8). Since this ubiquitous transporter(s) has been implicated in a number of diverse physiological processes, including cellular proliferation (reviewed in reference 9), these authors suggested that this enhanced Na'-H' exchange might underlie known complications of the diabetic state such as renal hypertrophy (7,8).…”

Section: Introductionmentioning

confidence: 99%

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Correction of enhanced Na(+)-H+ exchange of rat small intestinal brush-border membranes in streptozotocin-induced diabetes by insulin or 1,25-dihydroxycholecalciferol.

et al. 1991

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Diabetes was induced in rats by administration of a single i.p. injection of streptozotocin (50 mg/kg body wt). After 7 d, diabetic rats were further treated with insulin or 1,25-dihydroxycholecalciferol [1,25(0H)2D3J for an additional 5-7 d. Control, diabetic, diabetic + insulin, and diabetic + 1,25(OH)2D3 rats were then killed, their proximal small intestines were removed, and villus-tip epithelial cells were isolated and used to prepare brush-border membrane vesicles. Preparations from each of these groups were then analyzed and compared with respect to their amiloride-sensitive, electroneutral Na+-H+ exchange activity, using 22Na uptake as well as acridine orange techniques.The results of these experiments demonstrated that (a) H+ gradient-dependent 22Na uptake as well as Na+ gradient-dependent transmembrane H+ fluxes were significantly increased in diabetic vesicles compared to their control counterparts, (b) kinetic studies demonstrated that this enhanced 'Na uptake in diabetes was a result of increased maximal velocity (V.,.) of this exchanger with no change in apparent affinity (K.) for Na+, (c) serum levels of 1,25(OH)2D3 were significantly lower in diabetic animals compared with their control counterparts; and (d) insulin or 1,25(OH)2D3 treatment restored the V., alterations to control values, without any significant changes in K., concomitant with significantly increasing the serum levels of 1,25(OH)2D3 in diabetic animals. These results indicate that Na+-H+ activity is significantly increased in proximal small intestinal luminal membranes of streptozotocin-induced diabetic rats. Moreover, alterations in the serum levels of 1,25(0H)2D3 may, at least in part, explain this enhanced antiporter activity and its correction by insulin. (J. Clin. Invest.

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“…Previous studies have shown perturbations in ion transport in both the periphery and the brain during diabetes (1)(2)(3). Though diabetes is a vascular disease, little is known regarding the effects of diabetes on the blood-brain barrier (BBB) or the blood-cerebrospinal fluid barrier (BCSFB).…”

mentioning

confidence: 99%

Differential Effects of Diabetes on Rat Choroid Plexus Ion Transporter Expression

Egleton

Campos²,

Huber³

et al. 2003

Diabetes

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Though diabetes is a disease with vascular complications, little is known about its effects on the blood-brain barrier or the blood-cerebrospinal fluid barrier (BCSFB). The BCSFB is situated at choroid plexuses located in the lateral, third, and fourth ventricles. Choroid plexuses are the primary site of cerebrospinal fluid (CSF) production and express numerous ion transporters. Previous studies have shown a perturbation of ion transport in the periphery and brain during diabetes. In this study, we investigated the effect of diabetes on ion transporters in the choroid plexuses of streptozotocin (STZ)-induced diabetic rats. Diabetes was induced in male Sprague-Dawley rats by intraperitoneal injection of STZ (60 mg/kg in citrate buffer, confirmed by glucose analysis: 601 ؎ 22 mg/dl diabetic rats, 181 ؎ 46 mg/dl age-matched controls); and at 28 days, rats were killed, choroid plexuses harvested, and protein extracted. Western blot analyses were carried out using antibodies for ion transporters, including Na ؉ -K ؉ -2Cl ؊ cotransporter and the Na iabetes is a disease with numerous vascular complications. Previous studies have shown perturbations in ion transport in both the periphery and the brain during diabetes (1-3). Though diabetes is a vascular disease, little is known regarding the effects of diabetes on the blood-brain barrier (BBB) or the blood-cerebrospinal fluid barrier (BCSFB). It has been reported that diabetes is a risk factor not only for stroke (4,5), but also for normal-pressure hydrocephalus (6,7). Hydrocephalus is caused by excessive retention or production of cerebrospinal fluid (CSF) within the central nervous system. CSF is produced by the choroidal epithelial cells of the choroid plexus (8). The choroid plexuses are also the site of the BCSFB and are located in the lateral, third, and fourth ventricles. Capillaries of the choroid plexus are fenestrated, allowing extracellular fluid formation (unlike other brain capillary beds). CSF production involves the combination of a number of transport systems in the choroid plexus (9) (Fig. 1).Animal models of diabetes have shown that the Na (13), and Na ϩ -K ϩ -ATPase (14 -17) have altered expression and activity in a number of vascular beds. These three transporters are critical for CSF production and pH maintenance (9). In this study, we have investigated the effects of the streptozotocin (STZ) model of type 1 diabetes on expression of the Na ϩ -H ϩ exchanger, NaϪ cotransporter, and Na ϩ -K ϩ -ATPase in the rat choroid plexus. RESEARCH DESIGN AND METHODS Induction of diabetes.All protocols used in this study were approved by the University of Arizona Institutional Animal Care and Use Committee and abide by National Institutes of Health guidelines. Diabetes was induced in male 300-to 325-g Sprague-Dawley rats (Harlan, Indianapolis, IN) via an intraperitoneal injection of 60 mg/kg STZ (Sigma, St. Louis, MO) in sterile phosphate buffered saline. Control animals were injected intraperitoneally with phosphate buffered saline. The animals were housed under ...

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Na+-H+ exchange and Na+-dependent transport systems in streptozotocin diabetic rat kidneys

Cited by 17 publications

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Effect of thyroparathyroidectomy on urinary acidification in diabetic rats

Effect of thyroparathyroidectomy on urinary acidification in diabetic rats

Correction of enhanced Na(+)-H+ exchange of rat small intestinal brush-border membranes in streptozotocin-induced diabetes by insulin or 1,25-dihydroxycholecalciferol.

Differential Effects of Diabetes on Rat Choroid Plexus Ion Transporter Expression

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