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High glucose inhibits HCO −3 and fluid secretion in rat pancreatic ducts

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Abstract

Cellular mechanisms underlying the impairment of pancreatic fluid and electrolyte secretion in diabetes were examined using interlobular ducts isolated from rat pancreas. Fluid secretion was assessed by monitoring changes in luminal volume. HCO −3 uptake across the basolateral membrane was estimated from the recovery of intracellular pH following an acid load. Exposure to high glucose concentrations inhibited fluid secretion and reduced the rate of basolateral HCO −3 uptake in secretin-stimulated ducts isolated from normal rats. In ducts isolated from streptozotocin-treated diabetic rats, fluid secretion and basolateral HCO −3 uptake were also severely impaired but could be largely reversed by incubation in normal-glucose solutions. Sodium-dependent glucose cotransporter 1 (SGLT1), glucose transporter (GLUT)1, GLUT2, and GLUT8 transcripts were detected by reverse transcriptase polymerase chain reaction in isolated ducts. Raising the luminal glucose concentration in microperfused ducts caused a depolarization of the membrane potential, consistent with the presence of SGLT1 at the apical membrane. Unstimulated ducts filled with high-glucose solutions lost luminal fluid by a phlorizin-sensitive mechanism, indicating that pancreatic ducts are capable of active glucose reabsorption from the lumen via SGLT1. In ducts exposed to high glucose concentrations, continuous glucose diffusion to the lumen and active reabsorption via SGLT1 would lead to elevation of intracellular Na+ concentration and sustained depolarization of the apical membrane. These two factors would tend to inhibit the basolateral uptake and apical efflux of Cl− and HCO −3 and could therefore account for the impaired fluid and electrolyte secretion that is observed in diabetes.

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Acknowledgements

This work was supported by grants from the Japanese Society for the Promotion of Science and the Ministry of Health, Labor, and Welfare, Japan. We thank Dr. A. K. Stewart for helpful discussions.

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Authors and Affiliations

  1. Department of Gastroenterology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan

    Sachiko Futakuchi, Shigeru B. H. Ko & Hidemi Goto

  2. Department of Human Nutrition, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan

    Hiroshi Ishiguro, Akiko Yamamoto, Miyuki Nakakuki, Ying Song & Takaharu Kondo

  3. Miyoshi Municipal Hospital, Miyoshi, Aichi, 470-0224, Japan

    Satoru Naruse

  4. Nagoya University of Arts and Sciences, Nisshin, Aichi, 470-0196, Japan

    Kotoyo Fujiki

  5. Faculty of Life Sciences, University of Manchester, Manchester, M13 9NT, UK

    Martin C. Steward

  6. Research Center of Health, Physical Fitness, and Sports, Nagoya University, (Human Nutrition, Nagoya University Graduate School of Medicine), Furo-cho E5-2 (130), Chikusa-ku, Nagoya, 464-8601, Japan

    Hiroshi Ishiguro

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  1. Sachiko Futakuchi
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  2. Hiroshi Ishiguro
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  4. Shigeru B. H. Ko
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  7. Miyuki Nakakuki
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  8. Ying Song
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  9. Martin C. Steward
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  10. Takaharu Kondo
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  11. Hidemi Goto
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Correspondence to Hiroshi Ishiguro.

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Futakuchi, S., Ishiguro, H., Naruse, S. et al. High glucose inhibits HCO −3 and fluid secretion in rat pancreatic ducts. Pflugers Arch - Eur J Physiol 459, 215–226 (2009). https://doi.org/10.1007/s00424-009-0731-6

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  • DOI: https://doi.org/10.1007/s00424-009-0731-6

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