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      Effect of Cyclosporine A on Glucose Interstitial Concentration in Renal Cortex and Medulla from Rats

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          Aim: To standardize microdialysis in rat kidneys and address cyclosporine A (CsA) effects on renal cortex and medulla interstitial glucose. Methods: Munich-Wistar rats were treated with vehicle or CsA (15 mg/kg/day) for 3 weeks. Glucose was assessed by spectrophotometry in dialysate samples from cortex, medulla and arterial plasma. Plasma insulin was measured by radioimmunoassay. Renal blood flow (RBF) was measured by Doppler ultrasound. Creatinine and urea were measured by spectrophotometry. Results: CsA significantly increased the plasma levels of urea and creatinine (1.5 ± 0.20 vs. 0.73 ± 0.03 mg/dl in controls, p < 0.05). Medullary glucose in control was 44% lower than arterial glucose (56 ± 6 vs. 101 ± 8 mg/dl, p < 0.05). At the same time, CsA increased arterial (163 ± 35 vs. 101 ± 8 mg/dl in controls, p < 0.05) and medullary interstitial glucose (100 ± 18 vs. 56 ± 6 mg/dl in controls, p < 0.05), but did not affect cortical glucose (114 ± 21 vs. 90 ± 11 mg/dl in controls). These changes occurred in the presence of a decreased plasma insulin level (2.7 ± 0.2 vs. 9.3 ± 0.4 µU/ml in controls, p < 0.05). The increment in medullary glucose in CsA group occurred despite a reduction in RBF (4.6 ± 0.8 vs. 6.5 ± 1.0 ml/min/kidney in controls, p < 0.05). Conclusions: Microdialysis was an adequate tool to investigate in vivo regulation of renal glucose metabolism. Renal glucose uptake was dependent on medullary cells and CsA treatment induced diabetogenic effects on renal medulla in situ.

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          Most cited references 28

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          Renal gluconeogenesis: its importance in human glucose homeostasis.

          Studies conducted over the last 60 years in animals and in vitro have provided considerable evidence that the mammalian kidney can make glucose and release it under various conditions. Until quite recently however, it was generally believed that the human kidney was not an important source of glucose except during acidosis and after prolonged fasting. This review will summarize early work in animals and humans, discuss methodological problems in assessing renal glucose release in vivo, and present results of recent human studies that provide evidence that the kidney may play a significant role in carbohydrate metabolism under both physiological and pathological conditions.
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            Microdialysis--principles and applications for studies in animals and man.

             U Ungerstedt (1991)
            Microdialysis is a technique for sampling the chemistry of the individual tissues and organs of the body, and is applicable to both animal and human studies. The basic principle is to mimic the function of a capillary blood vessel by perfusing a thin dialysis tube implanted into the tissue with a physiological liquid. The perfusate is analysed chemically and reflects the composition of the extracellular fluid with time due to the diffusion of substances back and forth over the membrane. Microdialysis is thus a technique whereby substances may be both recovered from and supplied to a tissue. The most important features of microdialysis are as follows: it samples the extracellular fluid, which is the origin of all blood chemistry; it samples continuously for hours or days without withdrawing blood; and it purifies the sample and simplifies chemical analysis by excluding large molecules from the perfusate. However, the latter feature renders the technique unsuitable for sampling large molecules such as proteins. The technique has been extensively used in the neurosciences to monitor neurotransmitter release, and is now finding application in monitoring of the chemistry of peripheral tissues in both animal and human studies.
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              Abnormal renal and hepatic glucose metabolism in type 2 diabetes mellitus.

              Release of glucose by liver and kidney are both increased in diabetic animals. Although the overall release of glucose into the circulation is increased in humans with diabetes, excessive release of glucose by either their liver or kidney has not as yet been demonstrated. The present experiments were therefore undertaken to assess the relative contributions of hepatic and renal glucose release to the excessive glucose release found in type 2 diabetes. Using a combination of isotopic and balance techniques to determine total systemic glucose release and renal glucose release in postabsorptive type 2 diabetic subjects and age-weight-matched nondiabetic volunteers, their hepatic glucose release was then calculated as the difference between total systemic glucose release and renal glucose release. Renal glucose release was increased nearly 300% in diabetic subjects (321+/-36 vs. 125+/-15 micromol/min, P < 0.001). Hepatic glucose release was increased approximately 30% (P = 0.03), but increments in hepatic and renal glucose release were comparable (2.60+/-0.70 vs. 2.21+/-0.32,, respectively, P = 0.26). Renal glucose uptake was markedly increased in diabetic subjects (353+/-48 vs. 103+/-10 micromol/min, P < 0.001), resulting in net renal glucose uptake in the diabetic subjects (92+/-50 micromol/ min) versus a net output in the nondiabetic subjects (21+/-14 micromol/min, P = 0.043). Renal glucose uptake was inversely correlated with renal FFA uptake (r = -0.51, P < 0.01), which was reduced by approximately 60% in diabetic subjects (10. 9+/-2.7 vs. 27.0+/-3.3 micromol/min, P < 0.002). We conclude that in type 2 diabetes, both liver and kidney contribute to glucose overproduction and that renal glucose uptake is markedly increased. The latter may suppress renal FFA uptake via a glucose-fatty acid cycle and explain the accumulation of glycogen commonly found in the diabetic kidney.

                Author and article information

                Am J Nephrol
                American Journal of Nephrology
                S. Karger AG
                May 2006
                02 June 2006
                : 26
                : 2
                : 163-169
                aLaboratory of Endocrinology and Metabolism, Department of Molecular Biology, bDivision of Nephrology, São José do Rio Preto Medical School, São Paulo, and cDepartment of Immunology, Physiology and Biochemistry, University of São Paulo, Ribeirão Preto Medical School, São Paulo, Brazil
                92983 Am J Nephrol 2006;26:163–169
                © 2006 S. Karger AG, Basel

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                Page count
                Figures: 4, References: 40, Pages: 7
                Self URI (application/pdf):
                Original Report: Laboratory Investigation

                Cardiovascular Medicine, Nephrology

                Microdialysis, Nephrotoxicity, Kidney, Glucose, Cyclosporine, Diabetes


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