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

  • Renal Function, Body Fluids
  • Published:
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Abstract

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 μU/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 μM) (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 μM) or colchicine (50–100 μM), whereas it was abolished by cytochalasin D or latrunculin B (both 1 μM). 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 μM) 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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Acknowledgements

We thank Dr. Pablo Damiano and Dr. Liliana Karabatas for skillful assistance with blood pressure and insulin measurements. This project was supported by grants from the Ministerio de Salud de la Nación, Becas de Investigación “Ramón Carrillo–Arturo Oñativia” (2000–2001); Agencia Nacional de Promoción Científica y Técnica (PICT 05–08658); and CONICET PIP573. M.B. Barontini, C.F. Mendez and S. Nowicki are Senior Investigators from CONICET, Argentina.

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Authors and Affiliations

  1. Centro de Investigaciones Endocrinológicas (CONICET), Hospital de Niños R. Gutierrez, Gallo 1360 (C1425EFD) , Buenos Aires, Argentina

    Andrea Carranza, Marta Barontini & Susana Nowicki

  2. Departamento de Bioquímica Humana, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155 (C1121ABG), Buenos Aires, Argentina

    Carlos F. Mendez

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  1. Andrea Carranza
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  2. Carlos F. Mendez
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  3. Marta Barontini
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  4. Susana Nowicki
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Correspondence to Susana Nowicki.

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Carranza, A., Mendez, C.F., Barontini, M. et al. Insulin enhances l-dopa renal proximal tubule uptake: a regulatory mechanism impaired in insulin resistance. Pflugers Arch - Eur J Physiol 448, 85–92 (2004). https://doi.org/10.1007/s00424-003-1220-y

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  • DOI: https://doi.org/10.1007/s00424-003-1220-y

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