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To address the hypothesis that functional changes in tissue transport can be related to structural alterations, we combined mathematical modeling with in vivo experimentation. The model concept includes interstitial diffusion and removal by a distributed microvasculature. Transport of solute and water across the peritoneum is measured via a plastic chamber affixed to the abdominal wall of anesthetized Sprague-Dawley rats. Solutions containing [(14)C]mannitol, with or without vasoactive compounds [control (C; n = 10), C + nitroprusside (NP; n = 10), C + norepinephrine (NE; n = 10)], were infused into the chamber, and the volume and tracer concentrations were determined over 60 min to calculate the mass transfer coefficient (MTC) and the water flux. At 60 min, FITC-dextran (500 kDa) was given to mark the perfused vasculature. After euthanasia, the tissue under the chamber was frozen, dried, sliced with a cryomicrotome, and examined with fluorescent microscopy and quantitative autoradiography. The microvessel density (x10(3)/cm(2): NE, 50 +/- 10; C, 180 +/- 7.0; NP, 225 +/- 15) resulted in marked differences (P < 0.05) in water flux (mul.min(-1).cm(-2): NE, 0.1 +/- 0.1; C, 1.6 +/- 0.4; NP, 1.0 +/- 0.2) and in mannitol MTC (x10(3) cm/min: NE, 0.9 +/- 0.3; C, 3.8 +/- 0.3; NP, 3.6 +/- 0.6). Concentration profiles and calculated capillary permeability and tissue diffusivity were significantly different among the groups. These results demonstrate a direct correlation of mass transfer, diffusion, capillary permeability, and water flux with peritoneal vascular density and validate a method by which mechanistic changes in transport may be measured.

Butyrate enemas have been demonstrated to ameliorate inflammation in ulcerative colitis. The mechanism of this protective effect of butyrate is not known, and this study examines the effect of butyrate on epithelial function, inducible heat shock protein 70 (HSP70) expression, and NF-kappaB activation in experimental colitis. Colitis was induced in rats by oral dextran sulfate sodium (DSS) and by butyrate or saline enemas. Mucosal barrier function was assessed by electrical resistance and [14C]mannitol permeability. HSP70 production was determined by [35S]methionine labeling, Western blot analysis, and immunohistochemistry. Activation of heat shock factors (HSFs) and NF-kappaB was evaluated by EMSA. Butyrate showed a significant protection against the decrease in cell viability, increase in mucosal permeability, and polymorphonuclear neutrophil infiltration seen in DSS colitis. Butyrate inhibited HSP70 expression in DSS colitis and also inhibited the activation of HSF and NF-kappaB. Thus butyrate enema was found to be cytoprotective in DSS colitis, an effect partly mediated by suppressing activation of HSP70 and NF-kappaB.

Skeletal muscle glucose uptake requires delivery of glucose to the sarcolemma, transport across the sarcolemma, and the irreversible phosphorylation of glucose by hexokinase (HK) inside the cell. Here, a novel method was used in the conscious rat to address the roles of these three steps in controlling the rate of glucose uptake in soleus, a muscle comprised of type I fibers, and two muscles comprised of type II fibers. Experiments were performed on conscious rats under basal conditions or during hyperinsulinemic euglycemic clamps. Rats received primed, constant infusions of 3-O-methyl-[3H]glucose (3-O-MG) and [1-14C]mannitol. Total muscle glucose concentration and the steady-state ratio of intracellular to extracellular 3-O-MG concentration, which distributes based on the transsarcolemmal glucose gradient (TSGG), were used to calculate glucose concentrations at the inner and outer sarcolemmal surfaces ([G](im) and [G](om), respectively) in muscle. Muscle glucose uptake was much lower in muscle comprised of type II fibers than in soleus under both basal and insulin-stimulated conditions. Under all conditions, the TSGG in type II muscle exceeded that in soleus, indicating that glucose transport plays a more important role to limit glucose uptake in type II muscle. Although hyperinsulinemia increased [G](im) in soleus, indicating that phosphorylation was a limiting factor, type II muscle was limited primarily by glucose delivery and glucose transport. In conclusion, the relative importance of glucose delivery, transport, and phosphorylation in controlling the rate of insulin-stimulated muscle glucose uptake varies between muscle fiber types, with glucose delivery and transport being the primary limiting factors in type II muscle.