Small intestine hexose transport in experimental diabetes. Increased transporter mRNA and protein expression in enterocytes.

Burant, Charles F.; Flink, Susan; DePaoli, Alexander; Chen, Janet; Lee, Wen Sen; Hediger, Matthias A.; Buse, John B.; Chang, Eugene B.

doi:10.1172/jci117010

Cited by 139 publications

(89 citation statements)

References 29 publications

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“…Although the dual tracer approach used in the present experiments cannot distinguish between these two processes, the portal rate of appearance of enterically delivered glucose was slightly (but not significantly) lower in the diabetic subjects than in the nondiabetic subjects. This contrasts with reports that glucose absorption (25) and intestinal transport (49,50) are enhanced in chronically diabetic animals. Although this could be due to a species difference, it more likely is because the diabetic animals generally were severely hyperglycemic and hyperphagic, which presumably led to intestinal hypertrophy (51).…”

Section: Discussioncontrasting

confidence: 98%

Type 2 Diabetes Impairs Splanchnic Uptake of Glucose but Does Not Alter Intestinal Glucose Absorption During Enteral Glucose Feeding

et al. 2001

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We have previously reported that splanchnic glucose uptake, hepatic glycogen synthesis, and hepatic glucokinase activity are decreased in people with type 2 diabetes during intravenous glucose infusion. To determine whether these defects are also present during more physiological enteral glucose administration, we studied 11 diabetic and 14 nondiabetic volunteers using a combined organ catheterization-tracer infusion technique. Glucose was infused into the duodenum at a rate of 22 mol ⅐ kg ؊1 ⅐ min ؊1 while supplemental glucose was given intravenously to clamp glucose at ϳ10 mmol/l in both groups. Endogenous hormone secretion was inhibited with somatostatin, and insulin was infused to maintain plasma concentrations at ϳ300 pmol/l (i.e., twofold higher than our previous experiments). Total body glucose disappearance, splanchnic, and leg glucose extractions were markedly lower (P < 0.01) in the diabetic subjects than in the nondiabetic subjects. UDP-glucose flux, a measure of glycogen synthesis, was ϳ35% lower (P < 0.02) in the diabetic subjects than in the nondiabetic subjects. This was entirely accounted for by a decrease (P < 0.01) in the contribution of extracellular glucose because the contribution of the indirect pathway to hepatic glycogen synthesis was similar between groups. Neither endogenous and splanchnic glucose productions nor rates of appearance of the intraduodenally infused glucose in the portal vein differed between groups. In summary, both muscle and splanchnic glucose uptake are impaired in type 2 diabetes during enteral glucose administration. The defect in splanchnic glucose uptake appears to be due to decreased uptake of extracellular glucose, implying decreased glucokinase activity. Thus, abnormal hepatic and muscle (but not gut) glucose metabolism are likely to contribute to postprandial hyperglycemia in people with type 2 diabetes. Diabetes 50:1351-1362, 2001

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Section: Discussioncontrasting

confidence: 98%

Type 2 Diabetes Impairs Splanchnic Uptake of Glucose but Does Not Alter Intestinal Glucose Absorption During Enteral Glucose Feeding

et al. 2001

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“…Results from the present study show that the villus distribution of GLUT1 was similar to that reported for the other two enterocyte transporters, GLUT2 and SGLT1 [5]. In all cases, the progressive maturation of cells during their migration along the villus results in maximal expression of transport protein in the mid-villus region.…”

Section: Discussionsupporting

confidence: 86%

“…Recent studies have found raised enterocyte levels of SGLT1 [4,5] and the facilitated transporter GLUT2 [5] in streptozotocin (STZ)-treated rats and increased expression of these proteins are now known to be involved in the enhanced glucose transport at the BBM and BLM, respectively.…”

Section: Animalsmentioning

confidence: 99%

Streptozotocin diabetes and the expression of GLUT1 at the brush border and basolateral membranes of intestinal enterocytes

et al. 1996

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Changes in membrane expression of sodium-dependent glucose transporter (SGLTI) and glucose transporter isoform (GLUT2) protein have been implicated in the increased intestinal glucose transport in streptozotocin-diabetes. The possible involvement of GLUT1 in the transport response, however, has not previously been studied. Using confocal microscopy on tissue sections and Western blotting of purified brush border membrane (BBM) and basolateral membrane (BLM), we have examined enterocyte expression of GLUTI in untreated and in 1 and 21 day streptozotocin diabetic rats. In control enterocytes, GLUT1 was absent at the BBM and detected at low levels at the BLM. Diabetes resulted in a 4-to 5-fold increased expression of GLUT1 at the BLM and the protein could also be readily detected at the BBM. Insulin treatment of diabetic rats increased GLUT1 level at the BBM but was without effect on expression of the protein at the BLM.

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“…GLUT8 (16) was present at approximately the same low level in control and mutant intestine, and GLUT9 (19) was not expressed (not shown). Expression of GLUT5, a fructose transporter located in the apical membrane of epithelial cells (20,21) and whose expression is known to be up-regulated in diabetes (22), was increased, however.…”

Section: Resultsmentioning

confidence: 98%

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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Small intestine hexose transport in experimental diabetes. Increased transporter mRNA and protein expression in enterocytes.

Cited by 139 publications

References 29 publications

Type 2 Diabetes Impairs Splanchnic Uptake of Glucose but Does Not Alter Intestinal Glucose Absorption During Enteral Glucose Feeding

Type 2 Diabetes Impairs Splanchnic Uptake of Glucose but Does Not Alter Intestinal Glucose Absorption During Enteral Glucose Feeding

Streptozotocin diabetes and the expression of GLUT1 at the brush border and basolateral membranes of intestinal enterocytes

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

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