Urinary sorbitol measurement and the effect of an aldose reductase inhibitor on its concentration in the diabetic state

Nakano, Itsuko; Tsugawa, Toru; Shinohara, Rikio; Watanabe, Fumio; Fujita, Takashi; Nagata, Minoru; Kato, Takefumi; Himeno, Yumiko; Kobayashi, Takako; Fujiwara, Kentaro; Nagata, Mutsuko; Itoh, Mitsuyasu; Nagasaka, Akio

doi:10.1016/s1056-8727(02)00169-1

Cited by 10 publications

(8 citation statements)

References 18 publications

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“…5 shows the fluorescence intensity versus the variation in the concentration of β-NAD + . 10 Thus, a photomultiplier tube was required for measuring at low concentration of sorbitol. For low concentrations of β-NAD + , the enzymatic reaction rate and the NADH production decreased.…”

Section: Optimization Of the Sorbitol Biosensormentioning

confidence: 99%

A fiber-optic sorbitol biosensor based on NADH fluorescence detection toward rapid diagnosis of diabetic complications

Gessei

Arakawa

Kudo

et al. 2015

Analyst

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Accumulation of sorbitol in the tissue is known to cause microvascular diabetic complications. In this paper, a fiber-optic biosensor for sorbitol which is used as a biomarker of diabetic complications was developed and tested. The biosensor used a sorbitol dehydrogenase from microorganisms of the genus Flavimonas with high substrate specificity and detected the fluorescence of reduced nicotinamide adenine dinucleotide (NADH) by the enzymatic reaction. An ultraviolet light emitting diode (UV-LED) was used as the excitation light source of NADH. The fluorescence of NADH was detected using a spectrometer or a photomultiplier tube (PMT). The UV-LED and the photodetector were coupled using a Y-shaped optical fiber. In the experiment, an optical fiber probe with a sorbitol dehydrogenase immobilized membrane was placed in a cuvette filled with a phosphate buffer containing the oxidized form of nicotinamide adenine dinucleotide (NAD + ). The changes in NADH fluorescence intensity were measured after adding a standard sorbitol solution. According to the experimental assessment, the calibration range of the sorbitol biosensor systems using a spectrometer and a PMT was 5.0-1000 µmol L −1 and 1.0-1000 µmol L −1 , respectively. The sorbitol biosensor system using the sorbitol dehydrogenase from microorganisms of the genus Flavimonas has high selectivity and sensitivity compared with that from sheep liver. The sorbitol biosensor allows for point-of-care testing applications or daily health care tests for diabetes patients.

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Section: Optimization Of the Sorbitol Biosensormentioning

confidence: 99%

A fiber-optic sorbitol biosensor based on NADH fluorescence detection toward rapid diagnosis of diabetic complications

Gessei

Arakawa

Kudo

et al. 2015

Analyst

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“…We have previously reported an improved fluorometric and enzymatic method for measuring urinary sorbitol concentrations, which showed good sensitivity and reproducibility (Nakano et al 2003) and confirmed that urinary sorbitol excretion and whole blood sorbitol levels in diabetic patients were significantly higher than those in nondiabetic controls, and that the difference was more significant in urine than in whole blood (Nakano et al 2003). In the present study, we measured urinary sorbitol and NAG excretion as well as whole blood sorbitol concentration, and evaluated their correlation with AR activity in spontaneously generated diabetic WBN-kob rats.…”

Section: Discussionmentioning

confidence: 99%

“…To estimate the glucose metabolic state of the whole body and peripheral tissues, many investigators have determined sorbitol levels in various tissues, such as the erythrocytes, peripheral nerves, the lens, the retina and renal tissues, and analyzed the correlation between sorbitol levels and diabetic complications (Malone et al 1980, Greene et al 1985, Naeser & Brolin 1991, Stevens et al 1995. Elevated levels of urinary sorbitol excretion measured by gas chromatography (Yoshii et al 2001) or using the improved method (Nakano et al 2003) were also observed in the diabetic patient.…”

Section: Introductionmentioning

confidence: 99%

Alteration of urinary sorbitol excretion in WBN-kob diabetic rats - treatment with an aldose reductase inhibitor

Tsugawa

Shinohara

Nagasaka

et al. 2004

Journal of Endocrinology

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An accerelated polyol pathway in diabetes contributes to the development of diabetic complications. To elucidate diabetic nephropathy involving also renal tubular damage, we measured urinary sorbitol concentration concomitantly with urinary N-acetyl--glucosaminidase (NAG) excretion in WBN-kob diabetic rats.Twenty-four-hour urinary sorbitol concentrations increased in the diabetic rats in parallel with whole blood sorbitol concentrations. An increase in 24-h urinary NAG excretion coincided with the elevated urinary sorbitol levels in the diabetic rats.The administration of epalrestat, an aldose reductase inhibitor, reduced the increased whole blood and urinary sorbitol concentrations and urinary NAG excretion concomitantly with renal aldose reductase inhibition in the diabetic rats.These results indicate that diabetic nephropathy involves distorted cell function of renal tubules, and that treatment with epalrestat may prevent at least the progress of the nephropathy.

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“…As for the available clinical data, it has been previously reported that blood and serum sorbitol levels are higher in diabetic patients versus healthy participants, 15 – 17 an observation consistent with increased flux through the polyol pathway. Hayashi et al 15 also showed a significant correlation between erythrocyte sorbitol concentrations and both blood glucose levels and HbA1c concentrations.…”

mentioning

confidence: 83%

Pharmacokinetics, Pharmacodynamics, Tolerability, and Safety of a Novel Sorbitol Dehydrogenase Inhibitor in Healthy Participants

Landau

Novotny

Preston

et al. 2010

The Journal of Clinical Pharma

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Increased glucose flux through the polyol pathway and the resultant oxidative stress is thought to be a major mechanistic contributor to microvascular diabetic complications. Inhibition of flux through this pathway can be blocked through inhibition of either of 2 enzymes, aldose reductase (AR) or sorbitol dehydrogenase (SDH). This report describes the pharmacokinetics, biomarker pharmacodynamics, and safety of CP-642,931, a potent and specific sorbitol dehydrogenase inhibitor (SDI). CP-642,931 was administered for 7 days to 57 healthy volunteers in doses ranging from 1 to 35 mg daily. After the 35-mg dose, CP-642,931 showed a t((1/2)) of 20.1 hours and t(max) at 0.5 to 1.25 hours. After a 35-mg dose, maximum inhibition of SDH was 91% (on days 1 and 7), and maximum serum sorbitol increase was 152-fold on day 7 compared to control. Five participants discontinued the study due to adverse events, including myalgia, muscle spasm, and muscle fatigue. All symptoms resolved in all but 1 participant, who continued to report intermittent muscle fasciculations upon follow-up. In conclusion, CP-642,931 is a potent and specific SDI that is rapidly absorbed through the oral route and effectively inhibits SDH. However, the drug is not well tolerated due to adverse neuromuscular effects.

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Urinary sorbitol measurement and the effect of an aldose reductase inhibitor on its concentration in the diabetic state

Cited by 10 publications

References 18 publications

A fiber-optic sorbitol biosensor based on NADH fluorescence detection toward rapid diagnosis of diabetic complications

A fiber-optic sorbitol biosensor based on NADH fluorescence detection toward rapid diagnosis of diabetic complications

Alteration of urinary sorbitol excretion in WBN-kob diabetic rats - treatment with an aldose reductase inhibitor

Pharmacokinetics, Pharmacodynamics, Tolerability, and Safety of a Novel Sorbitol Dehydrogenase Inhibitor in Healthy Participants

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