Rat Small Intestine Is an Insulin-Sensitive Gluconeogenic Organ

Croset, Martine; Rajas, Fabienne; Zitoun, Carine; Hurot, Jean-Marc; Montano, Sandrine; Mithieux, Gilles

doi:10.2337/diabetes.50.4.740

Cited by 168 publications

(220 citation statements)

References 35 publications

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“…As shown in Fig. 2, both mRNA were found to be expressed at the same level in control and mutant mice, but at lower level than in liver of control mice, in agreement with published data (27,28).…”

Section: Resultssupporting

confidence: 91%

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

Stümpel

Burcelin

Jungermann

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

143

115

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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.

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Section: Resultssupporting

confidence: 91%

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

Stümpel

Burcelin

Jungermann

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

143

115

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“…It is likely that administered glycerol is converted to glucose in secondary gluconeogenic organs, e.g., the kidney or the intestine (19), compensating for the assumed defect in glycerol transport into the hepatocytes. Thus, our data reveal that the capacity to metabolize exogenous glycerol via an AQP9-independent pathway is substantial, although the relative contribution is difficult to estimate due to potential compensatory mechanisms in AQP9 Ϫ/Ϫ mice.…”

Section: Defective Glycerol Metabolism In Aqp9 Gene Knockout Micementioning

confidence: 99%

Defective glycerol metabolism in aquaporin 9 (AQP9) knockout mice

Rojek

Skowroński

Füchtbauer

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

273

256

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Aquaporin-9 (AQP9) is an aquaglyceroporin membrane channel shown biophysically to conduct water, glycerol, and other small solutes. Because the physiological role/s of AQP9 remain undefined and the expression sites of AQP9 remain incomplete and conflicting, we generated AQP9 knockout mice. In the absence of physiological stress, knockout mice did not display any visible behavioral or severe physical abnormalities. Immunohistochemical analyses using multiple antibodies revealed AQP9 specific labeling in hepatocytes, epididymis, vas deferens, and in epidermis of wild type mice, but a complete absence of labeling in AQP9 ؊/؊ mice. In brain, no detectable labeling was observed. Compared with control mice, plasma levels of glycerol and triglycerides were markedly increased in AQP9 ؊/؊ mice, whereas glucose, urea, free fatty acids, alkaline phosphatase, and cholesterol were not significantly different. Oral administration of glycerol to fasted mice resulted in an acute rise in blood glucose levels in both AQP9 ؊/؊ and AQP9 ؉/؊ mice, revealing no defect in utilization of exogenous glycerol as a gluconeogenic substrate and indicating a high gluconeogenic capacity in nonhepatic organs. Obese Lepr db /Lepr db AQP9 ؊/؊ and obese Lepr db /Lepr db AQP9 ؉/؊ mice showed similar body weight, whereas the glycerol levels in obese Lepr db /Lepr db AQP9 ؊/؊ mice were dramatically increased. Consistent with a role of AQP9 in hepatic uptake of glycerol, blood glucose levels were significantly reduced in Lepr db /Lepr db AQP9 ؊/؊ mice compared with Lepr db / Lepr db AQP9 ؉/؊ in response to 3 h of fasting. Thus, AQP9 is important for hepatic glycerol metabolism and may play a role in glycerol and glucose metabolism in diabetes mellitus.aquaglyceroporin ͉ diabetes mellitus ͉ leptin receptor

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“…GSD type 1a and type 1b respectively correspond to inherited mutations in the genes that encode the catalytic subunit (G6PC) and the transporter unit (G6PT) of the G6Pase system [1,2,5,6]. The G6pc gene is expressed in the liver, kidney, and intestine, and these are the only organs that release glucose into the blood circulation [7][8][9][10].…”

Section: Introductionmentioning

confidence: 99%