High glucose inhibits HCO 3 − 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.

The Divergence, Actions, Roles, and Relatives of Sodium-Coupled Bicarbonate Transporters

“…In isolated, perfused pancreatic ducts, high levels of luminal glucose lead to an accumulation of Na ϩ and membrane depolarization, via the action of the apical Na/glucose cotransporter SGLT1, in duct cells (307). The authors of the study suggest that elevated [Na ϩ ] i inhibits NBCe1-mediated influx of Na ϩ and HCO 3 Ϫ at the basolateral membrane, thereby contributing to the decreased pancreatic HCO 3 Ϫ secretion associated with diabetes.…”

The Plasma Membrane Potential and the Organization of the Actin Cytoskeleton of Epithelial Cells

“…Thus, in the acinar cells of parotid salivary glands, modifications in the potassium conductance of the apical membrane produce changes in the fluid flow via changes in the apical PMP [111–113]. In pancreatic acinar ducts, modifications in the apical depolarization mediated by the sodium-glucose cotransporter modulate the amount of basolateral uptake of chloride and bicarbonate [114]. Another example is given by the basolateral membranes of tracheal and intestinal cells, where potassium channels containing the KCNE family of β -subunits control the chloride flux via modifications in the basolateral PMP [115].…”

Dynamic Prediction of ICU Mortality Risk Using Domain Adaptation

“…The overall picture improved after the first 20 hours after admission, and the mortality risk has decreased significantly. Interesting to notice that our model was able to capture known but complex relationships, such as high glucose values inhibiting HCO3 [45]. Figure 8 shows a summary plot associated with a patient who has not survived hospitalization.…”