High glucose inhibits HCO3 and fluid secretion in rat pancreatic ducts

Sachiko Futakuchi, Hiroshi Ishiguro, Satoru Naruse, Shigeru Ko, Kotoyo Fujiki, Akiko Yamamoto, Miyuki Nakakuki, Ying Song, Martin C. Steward, Takaharu Kondo, Hidemi Goto

Research output: Contribution to journalArticle

11 Citations (Scopus)

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. HCO3 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 HCO3 uptake in secretin-stimulated ducts isolated from normal rats. In ducts isolated from streptozotocin-treated diabetic rats, fluid secretion and basolateral HCO3 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 C1 and HCO3- and could therefore account for the impaired fluid and electrolyte secretion that is observed in diabetes.

Original languageEnglish
Pages (from-to)215-226
Number of pages12
JournalPflugers Archiv European Journal of Physiology
Volume459
Issue number1
DOIs
Publication statusPublished - 2009 Nov
Externally publishedYes

Fingerprint

Fluids and Secretions
Pancreatic Ducts
Sodium-Glucose Transporter 1
Ducts
Rats
Glucose
Fluids
Sodium
Electrolytes
Membranes
Depolarization
Phlorhizin
Medical problems
Secretin
Facilitative Glucose Transport Proteins
Streptozocin
Reverse Transcriptase Polymerase Chain Reaction
Membrane Potentials
Pancreas
Polymerase chain reaction

Keywords

  • Glucose transport HCO Transport diabetes mellitus
  • Pancreatic duct cell

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Physiology (medical)
  • Medicine(all)

Cite this

High glucose inhibits HCO3 and fluid secretion in rat pancreatic ducts. / Futakuchi, Sachiko; Ishiguro, Hiroshi; Naruse, Satoru; Ko, Shigeru; Fujiki, Kotoyo; Yamamoto, Akiko; Nakakuki, Miyuki; Song, Ying; Steward, Martin C.; Kondo, Takaharu; Goto, Hidemi.

In: Pflugers Archiv European Journal of Physiology, Vol. 459, No. 1, 11.2009, p. 215-226.

Research output: Contribution to journalArticle

Futakuchi, S, Ishiguro, H, Naruse, S, Ko, S, Fujiki, K, Yamamoto, A, Nakakuki, M, Song, Y, Steward, MC, Kondo, T & Goto, H 2009, 'High glucose inhibits HCO3 and fluid secretion in rat pancreatic ducts', Pflugers Archiv European Journal of Physiology, vol. 459, no. 1, pp. 215-226. https://doi.org/10.1007/s00424-009-0731-6
Futakuchi, Sachiko ; Ishiguro, Hiroshi ; Naruse, Satoru ; Ko, Shigeru ; Fujiki, Kotoyo ; Yamamoto, Akiko ; Nakakuki, Miyuki ; Song, Ying ; Steward, Martin C. ; Kondo, Takaharu ; Goto, Hidemi. / High glucose inhibits HCO3 and fluid secretion in rat pancreatic ducts. In: Pflugers Archiv European Journal of Physiology. 2009 ; Vol. 459, No. 1. pp. 215-226.
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