The facilitated component of intestinal glucose absorption

Abstract

The debate over the mechanism of the passive component of glucose absorption Following the initial proposal of Crane et al. (1961), the mechanism of Na + -glucose cotransport became firmly established over the next 25 years; for a review, see Stevens et al. (1984). One simple, but vital, point for the debate over the passive component is that there was and remains common agreement that Na + -glucose cotransport saturates at 30-50 mM glucose in vivo. Yet there were numerous reports that glucose absorption increases almost linearly from 50 mM to several hundred millimolar (see Fordtran & Inglefinger, 1968). It appeared that there must be other mechanisms for the absorption of glucose.Indeed, there was already much evidence, accruing alongside and even predating this intense period of work on Na + -glucose cotransport, that there is also a significant passive component of glucose absorption. Many papers referred to K m values for glucose absorption of 100 mM or more (see Parsons & Prichard, 1966); typical data are to be found in Holdsworth & Dawson (1964), showing that glucose and fructose absorption increased almost linearly up to a concentration of 280 mM. As early as 1956, Fullerton & Parsons reported that glucose absorption in vivo comprised two components: one was constant and not associated with water absorption (now identified with SGLT1); the other was variable and approximately proportional to water absorption up to 246 mM. Manome & Kuriaki (1961) used phloridzin to inhibit Na + -glucose cotransport and showed that glucose absorption in vivo comprised phloridzinsensitive and phloridzin-insensitive components. Using this approach, Debnam & Levin (1975) defined glucose absorption as the sum of an active component saturating around 30-50 mM glucose, and a phloridzin-insensitive component described as 'passive' or 'diffusive', since it was broadly linear and appeared non-saturable; the passive component equalled the active one at about 26 mM and continued to increase up to 128 mM glucose. Ilundain et al. (1979) and Lostao et al. (1991) reported that the passive component was some 3-5 times greater than the active component at high glucose concentrations. One significant point is that all studies showing clear evidence for a significant passive component are in vivo studies. That suggests (with hindsight -see below) that there is a significant difference between in vivo and in vitro preparations.Nineteen eighty-seven was a pivotal year for studies of intestinal glucose absorption. Pappenheimer & Reiss (1987) proposed the theory of paracellular solvent drag as an explanation for the passive component of glucose absorption, and Hediger et al. (1987) cloned the Na + -glucose cotransporter SGLT1. The molecular era of intestinal glucose absorption had arrived and produced a profound change in the intellectual climate of the field, which was to ensure that the molecular biology of SGLT1 Over the last decade, a debate has developed about the mechanism of the passive or 'diffusive' component of intestinal glucose absor...

GLUT2 protein at the rat proximal tubule brush border membrane correlates with protein kinase C (PKC)-βl and plasma glucose concentration

“…However, the predicted K m values for these two transporters are 0.5 and 2 mmol/l for SGLT1 and SGLT2, respectively, and in the setting of a high filtered glucose concentration, as in uncontrolled diabetes, both transporters would be saturated. Therefore, GLUT2 in the kidney may be unregulated, as occurs in the small intestine [33], where high glucose concentrations 'sensed' by SGLT proteins lead to rapid insertion of GLUT2 into the BBM. With a predicted K m of 20 to 40 mmol/l [17], GLUT2 would provide a capacity for glucose absorption that is much higher than that of the SGLT proteins.…”

Localization of brain endothelial luminal and abluminal transporters with immunogold electron microscopy

“…including cytosol to membrane recycling in oocytes, 66 intestinal GLUT2 recruitment, 67 and translocation of GLUT1 in retinal capillary membranes 68,69 and mesangial cells. 70 PKC also regulates translocation of GLUT1 71 and GLUT4 in muscle 72,73 and fat cells.…”

Intestinal Sugar Absorption Is Regulated by Phosphorylation and Turnover of Protein Kinase C βII Mediated by Phosphatidylinositol 3-Kinase- and Mammalian Target of Rapamycin-dependent Pathways

“…We have proposed that the other is a facilitated component mediated by glucose-dependent activation and recruitment of GLUT2 to the brush-border membrane. GLUT2 recruitment correlates with SGLT1-dependent activation of PKC 1 ␤II (2) so that SGLT1 is now seen to exert an important regulatory role in addition to its established functions as a scavenger and transporter (1). Regulation of the facilitated component may also involve mitogen-activated protein (MAP) kinase-and PI3-kinase-dependent signaling pathways (3).…”

“…1). It is well established that one of these is an active component mediated by the Na ϩ /glucose cotransporter, SGLT1.…”