title: High glucose inhibits HCO3(-) and fluid secretion in rat pancreatic ducts.
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 Cl(-) and HCO3(-) and could therefore account for the impaired fluid and electrolyte secretion that is observed in diabetes.
authors.affiliation: Department of Gastroenterology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Futakuchi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ishiguro
authors.forename: Satoru
authors.initials: S
authors.lastname: Naruse
authors.forename: Shigeru B H
authors.initials: SB
authors.lastname: Ko
authors.forename: Kotoyo
authors.initials: K
authors.lastname: Fujiki
authors.forename: Akiko
authors.initials: A
authors.lastname: Yamamoto
authors.forename: Miyuki
authors.initials: M
authors.lastname: Nakakuki
authors.forename: Ying
authors.initials: Y
authors.lastname: Song
authors.forename: Martin C
authors.initials: MC
authors.lastname: Steward
authors.forename: Takaharu
authors.initials: T
authors.lastname: Kondo
authors.forename: Hidemi
authors.initials: H
authors.lastname: Goto
mesh_terms: D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000503:physiopathology; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials; D010183:Pancreatic Ducts / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012633:Secretin / Q000378:metabolism / Q000494:pharmacology; D051269:Sodium-Glucose Transporter 1 / Q000378:metabolism
chemical_list: D001639:Bicarbonates; C495676:Slc5a1 protein, rat; D051269:Sodium-Glucose Transporter 1; D012633:Secretin; D005947:Glucose