Unstirred layer and kinetics of electrogenic glucose absorption in the human jejunum in situ

Abstract

SUMMARY Using an electrical technique we estimated the thickness of the unstirred layer in the human jejunum during kinetic studies of electrogenic glucose absorption. The unstirred layer in seven healthy volunteers (632 + 24 ,um: mean + SEM) was significantly thicker than in 10 patients with active coeliac disease (442 + 23 ,um) but not significantly different in seven patients who had responded to treatment by gluten withdrawal (585 + 49 ,um). There were similar differences in the values of 'Apparent Km' for electrogenic glucose absorption between healthy control subjects (36 + 6 mM) active coeliac patients (11 1 mM) and treated coeliac patients (31 + 5 mM). The changes in PDmax however, showed a different pattern. The PDmax in the active coeliac group (6f8 + 0 7 mV) was lower than in controls (7-6 + 0-6 mV) but not significantly so, while the PDmax in the treated coeliac group (10-6 + 0 9 mV) was significantly higher than in both the active coeliac and control groups. It should be noted that both operational kinetic parameters obtained in the present study are much lower than those obtained previously (Read et al., 1976b) because of the use of siphonage. Analysis of the results using a computer simulation indicates that the reduction in Apparent Km in active coeliac disease can be caused by the interaction of the decreased maximal absorption rate for glucose (Jmax) with the attenuated unstirred layer. In these circumstances it is not necessary to postulate any change in the affinity of the transport mechanism for glucose ('Real Km'). It is remarkable that the disease process produces an Apparent Km which is much closer to the Real Km than that found in health.Part 1: Measurement of functional unstirred layer thicknessWe have previously described a technique for measuring changes in transmural potential difference (PD) across the human jejunum in vivo in response to infusion of solutions containing glucose (Read et al., 1974). Using this technique we observed that the operational kinetic parameters ('Apparent Km', PDmax) for the active electrogenic component of glucose absorption were significantly lower in untreated coeliac disease than in healthy controls (Read et al., 1976b). It is possible that these results could be caused by differences in the thickness of the layer of unstirred fluid which lies adjacent to the mucosal epithelium.In this present paper we used an electrical technique for estimating the thickness of this unstirred

Oral uptake of nanoparticles: human relevance and the role of in vitro systems

“…The firmly adherent mucus layer has been indicated as 107-155 and >200 µm (Forstner et al 1995;Gustafsson et al 2012;Huh et al 2003;Johansson 2014;Kerss et al 1982;Pullan et al 1994). Jejunum mucus in humans had a thickness of 632 µm as assessed by in vivo measurements (Read et al 1977), and the average thickness of the mucus layer in the oral cavity varied between 70 and 100 µm (Collins and Dawes 1987) (Fig. 1).…”

Use of maltose hydrolysis measurements to characterize the interaction between the aqueous diffusion barrier and the epithelium in the rat jejunum.

“…Previous attempts to measure the thickness of an unstirred layer in the human jejunum used several different techniques, and reported thicknesses have ranged from 600 m (11,12) to 40 m (13). As discussed above, the observed hydrolysis of low concentrations of maltose in the rat could not have occurred if the unstirred layer over the villous tips had been thicker than ‫ف‬ 20 m. Analysis of the absorption of low glucose concentrations in man indicated that the observed absorption rates could not have occurred if the unstirred layer were greater than 40-m thick (13).…”

Non-animal models of epithelial barriers (skin, intestine and lung) in research, industrial applications and regulatory toxicology

“…Not long after, many pharmaceutical scientists began using computer modeling to model biopharmaceutical and pharmacokinetic processes (Beckett and Tucker, 1968), including the kinetics of buccal absorption (Beckett and Pickup, 1975), as well as to solve intractable or difficult pharmacokinetic analysis of advanced models for oral absorption (Wagner, 1975). Later analyses included computer modeling of transport processes across human gastrointestinal epithelia, including the presence of an aqueous diffusion layer and saturable transport in the human jejunum (Read et al, 1977) and numerical simulation of differential equations describing absorption processes along the length of the intestine (Atkins, 1980). The principles applied in these studies then evolved to include digital computing and deconvolution methodology to assess gastric and intestinal absorption (Veng-Pedersen, 1987).…”