Decreased Tubular Uptake of &lt;i&gt;L&lt;/i&gt;-3,4-Dihydroxyphenylalanine in Streptozotocin-Induced Diabetic Rats

Carranza, Andrea; Karabatas, Liliana; Barontini, Marta; Armando, Inés

doi:10.1159/000050014

Cited by 17 publications

(17 citation statements)

References 18 publications

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“…Selective depletion of intrarenal dopamine production accelerated diabetic nephropathy in our studies, consistent with alterations in intrarenal dopamine production that has been previously reported in both experimental and human diabetic nephropathy (15,36,40–42). These studies further confirm that intrarenal dopamine plays an important modulatory role in development and progression of renal injury in diabetes.…”

Section: Discussionsupporting

confidence: 92%

“…Previous studies have suggested that abnormalities in the intrarenal dopaminergic system may be an underlying contributing factor to increased renal salt and water reabsorption in diabetes (15,16). Diabetes is characterized by elevated glomerular filtration rate (GFR) and sodium retention due to increased proximal reabsorption and reduced luminal NaCl delivery to the macula densa (17,18).…”

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confidence: 99%

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Intrarenal Dopamine Inhibits Progression of Diabetic Nephropathy

et al. 2012

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The kidney has a local intrarenal dopaminergic system, and in the kidney, dopamine modulates renal hemodynamics, inhibits salt and fluid reabsorption, antagonizes the renin-angiotensin system, and inhibits oxidative stress. The current study examined the effects of alterations in the intrarenal dopaminergic system on kidney structure and function in models of type 1 diabetes. We studied catechol-O-methyl-transferase (COMT)−/− mice, which have increased renal dopamine production due to decreased dopamine metabolism, and renal transplantation was used to determine whether the effects seen with COMT deficiency were kidney-specific. To determine the effects of selective inhibition of intrarenal dopamine production, we used mice with proximal tubule deletion of aromatic amino acid decarboxylase (ptAADC−/−). Compared with wild-type diabetic mice, COMT−/− mice had decreased hyperfiltration, decreased macula densa cyclooxygenase-2 expression, decreased albuminuria, decreased glomerulopathy, and inhibition of expression of markers of inflammation, oxidative stress, and fibrosis. These differences were also seen in diabetic mice with a transplanted kidney from COMT−/− mice. In contrast, diabetic ptAADC−/− mice had increased nephropathy. Our study demonstrates an important role of the intrarenal dopaminergic system to modulate the development and progression of diabetic kidney injury and indicate that the decreased renal dopamine production may have important consequences in the underlying pathogenesis of diabetic nephropathy.

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Section: Discussionsupporting

confidence: 92%

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confidence: 99%

Intrarenal Dopamine Inhibits Progression of Diabetic Nephropathy

et al. 2012

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“…Indeed, previous results from our laboratory have described an increased renal excretion of L-dopa in streptozotocin-induced diabetic rats [5].…”

Section: Introductionmentioning

confidence: 79%

“…Early studies demonstrated that the uptake of L-dopa into the proximal tubules is an active process, with high structural specificity [7]. In previous studies from our laboratory the transport of L-dopa into proximal tubules has been shown to be impaired in aged rats [2], inhibited by β 2 -adrenergic receptor signalling [6] and by high glucose [5]. The reabsorbed L-dopa is converted into dopamine by the cytoplasmic aromatic Lamino acid decarboxylase [23], the intracellular availability of L-dopa being the limiting step in renal dopamine synthesis [2,23].…”

Section: Introductionmentioning

confidence: 99%

Insulin enhances l-dopa renal proximal tubule uptake: a regulatory mechanism impaired in insulin resistance

Carranza

Méndez

Barontini

et al. 2004

Pfl�gers Archiv European Journal of Physiology

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A stimulatory role for insulin in the uptake of neutral amino acids has been reported for a variety of tissues. Here we examine the effect of insulin on L-dopa uptake by proximal tubule cells (PT cells) isolated from control and fructose-fed rats (FR-rats, 10% w/v fructose solution in tap water), a model of insulin resistance. Insulin (200 microU/ml) increased L-dopa uptake into PT cells by about 50% (705+/-186 vs.1117+/-140 pmol L-dopa/mg protein per minute) (p<0.05). The higher uptake correlated with a 40% increase in the number of high-affinity L-dopa transport sites (L-dopa 0.2 microM) (0.59+/-0.05 vs. 0.82+/-0.09 pmol L-dopa/mg protein per minute), without changing their affinity. The effect of insulin was not modified by ouabain (1 mM), nocodazole (1-10 microM) or colchicine (50-100 microM), whereas it was abolished by cytochalasin D or latrunculin B (both 1 microM). This suggests that the process is independent of Na(+),K(+)-ATPase activity or the microtubule network but that it requires the integrity of the actin cytoskeleton. L-dopa transport by the low-affinity transport sites (L-dopa 5 microM) was not affected by insulin, neither was the effect of insulin observed in PT cells isolated from FR-rats. In line with this, FR-rats showed lower renal L-dopa reabsorption as compared to control animals (81+/-4 vs. 51+/-9%). Taken together, our results support the involvement of insulin in the multifactorial regulation of renal L-dopa reabsorption.

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“…Diabetes mellitus is a complex of metabolic disease characterized by hyperglycemia, diminished insulin production, impaired insulin action, or a combination of both resulting in the inability of glucose to be transported from the blood stream into the tissues, which in turn results in high blood glucose levels and excretion of glucose in the urine [1]. Cell functions involved in the action of insulin receptor binding enzyme and transporter activities are controlled by membrane properties [2].…”

Section: Introductionmentioning

confidence: 99%