Normal kinetics of intestinal glucose absorption in the absence of GLUT2: evidence for a transport pathway requiring glucose phosphorylation and transfer into the endoplasmic reticulum.

Glucose is absorbed through the intestine by a transepithelial transport system initiated at the apical membrane by the cotransporter SGLT-1; intracellular glucose is then assumed to diffuse across the basolateral membrane through GLUT2. Here, we evaluated the impact of GLUT2 gene inactivation on this transepithelial transport process. We report that the kinetics of transepithelial glucose transport, as assessed in oral glucose tolerance tests, was identical in the presence or absence of GLUT2; that the transport was transcellular because it could be inhibited by the SGLT-1 inhibitor phlorizin, and that it could not be explained by overexpression of another known glucose transporter. By using an isolated intestine perfusion system, we demonstrated that the rate of transepithelial transport was similar in control and GLUT2(-/-) intestine and that it was increased to the same extent by cAMP in both situations. However, in the absence, but not in the presence, of GLUT2, the transport was inhibited dose-dependently by the glucose-6-phosphate translocase inhibitor S4048. Furthermore, whereas transport of [(14)C]glucose proceeded with the same kinetics in control and GLUT2(-/-) intestine, [(14)C]3-O-methylglucose was transported in intestine of control but not of mutant mice. Together our data demonstrate the existence of a transepithelial glucose transport system in GLUT2(-/-) intestine that requires glucose phosphorylation and transfer of glucose-6-phosphate into the endoplasmic reticulum. Glucose may then be released out of the cells by a membrane traffic-based pathway similar to the one we previously described in GLUT2-null hepatocytes.

Effect of somatostatin on duodenal glucose absorption in man.

OBJECTIVE: The hyperglycemic hyperinsulinemic clamp technique using intraduodenally infused glucose is an attractive tool for studying postprandial glucose metabolism under strictly controlled conditions. Because it requires the use of somatostatin (SST), we examined, in this study, the effect of SST on intestinal glucose absorption. CONTEXT: Twenty-six normal volunteers were given a constant 3-h intraduodenal infusion of glucose (6 mg.kg(-1).min(-1)) labeled with [2-(3)H]glucose for glucose absorption measurement. During glucose infusion, 19 subjects received iv SST at doses of 10-100 ng.kg(-1).min(-1) plus insulin and glucagon, and seven subjects were studied under control conditions. In the controls, glucose was absorbed at a rate that, after a 20-min lag period, equaled the infusion rate. RESULTS: With all the doses of SST tested, absorption was considerably delayed but equaled the rate of infusion after 3 h. At that time, only 5 +/- 2% of the total amount of infused glucose was unabsorbed in the control subjects vs. 36 +/- 2% (P < 0.001) in the SST-infused subjects. In the latter, the intraluminal residue was almost totally absorbed within 40 min of the cessation of SST infusion. At the lowest dose of SST tested (10 ng.kg(-1).min(-1)), suppression of insulin secretion was incomplete. CONCLUSION: These properties of SST hamper the use of intraduodenal hyperglycemic hyperinsulinemic clamps as a tool for exploring postprandial glucose metabolism.

An infrared reflection-absorption spectroscopic (IRRAS) study of the interaction of lipid A and lipopolysaccharide Re with endotoxin-binding proteins.

Lipopolysaccharides (LPS, endotoxins) are main constituents of the outer membranes of Gram-negative bacteria, with the 'endotoxic principle' lipid A anchoring LPS into the membrane. When LPS is removed from the bacteria by the action of the immune system or simply by cell dividing, it may interact strongly with immunocompetent cells such as mononuclear cells. This interaction may lead, depending on the LPS concentration, to beneficial (at low) or pathophysiological (at high concentrations) reactions, the latter frequently causing the septic shock syndrome. There is a variety of endogenous LPS-binding proteins. To this class belong lactoferrin (LF) and hemoglobin (Hb), which have been shown to suppress and enhance the LPS-induced cytokine secretion in mononuclear cells, respectively. To elucidate the interaction mechanisms of endotoxins with these proteins, we have investigated in an infrared reflection-absorption spectroscopy (IRRAS) study the interaction of LPS or lipid A monolayers at the air/water interface with LF and Hb proteins, injected into the aqueous subphase. The data are clearly indicative of completely different interaction mechanisms of the endotoxins with the proteins, with the LF acting only at the LPS backbone, whereas Hb incorporates into the lipid monolayer. These data allow an understanding of the different reactivities in the biomedicinal systems.

Littérature contemporaine et engagement : quand les textes interpellent la réalité postmoderne et néolibérale

La littérature peut‐elle s'engager pour un monde où le néolibéralisme s'est érigé en triomphe sur les décombres des idéologies rivales ? Où la postmodernité a laissé la société orpheline de ses anciens repères collectifs ? Fondée sur des questions liant le roman français contemporain et des courants de pensée tels que la postmodernité ou le néolibéralisme, cette thèse de doctorat propose une réflexion autour de l'engagement littéraire, dans son acception à la fin du XXe siècle ; autrement dit, une redéfinition de la notion en accord avec les enjeux socio‐économiques contemporains. « Que peut la littérature ? » demandait Sartre en 1947 : cette question, nous la portons sur la fin du XXe siècle. La première partie de cette étude s'intéresse aux écrivains contemporains et mesure les similitudes qui attestent d'une filiation avec la compréhension sartrienne de l'engagement littéraire ou, au contraire, les distinctions qui entérinent une rupture. La deuxième partie témoigne qu'il ne peut y avoir d'engagement littéraire sans prise en considération du monde. La postmodernité et le néolibéralisme : ces deux courants sont interrogés tour à tour dans leur spécificité propre, avant d'interroger la pertinence du rapprochement entre discours littéraire et socio‐économique. L'originalité de cette thèse est de proposer ensuite une définition de l'engagement littéraire contemporain, ainsi qu'une réflexion sur les conditions nécessaires à son expression. La troisième partie est consacrée aux formes littéraires. L'hypothèse faisant de la littérature le révélateur du « surplomb problématique » d'une époque (Wolfgang Iser) s'impose comme le fil conducteur qui relie les textes du corpus : l'agencement des thèmes, les personnages, les emprunts à différentes traditions et les registres de langue constituent autant de variations possibles inscrivant l'hypothèse d'un « individu travaillant » aliéné au sein du texte. Ouvriers, mais aussi employés du secteur tertiaire, ou cadres, reconquièrent par l'entremise de la fiction - qui les met en vedette - une partie de leur visibilité perdue dans la sphère publique.