Rapid insertion of GLUT2 into the rat jejunal brush-border membrane promoted by glucagon-like peptide 2

Au, Anita G.; Gupta, Alina; Schembri, Paul J; Cheeseman, Chris I.

doi:10.1042/bj20020393

Cited by 155 publications

(134 citation statements)

References 27 publications

Supporting

Mentioning

120

Contrasting

Unclassified

Order By: Relevance

“…2). The distinct banding patterns confirmed that there was no cross-reactivity between antibody to one transporter and the other transporter; in addition, antibody to a sequence within the extracellular loop of GLUT2 gave similar results to the C-terminal antibody (8). All bands were eliminated by preincubation of antiserum with excess of the corresponding antigenic peptide, confirming the specificity of GLUT5 and the GLUT2 antisera for their target transporters (data not shown).…”

Section: Resultssupporting

confidence: 61%

“…Support for the model of rapid, GLUT2-mediated up-regulation of sugar absorption has been provided by the observation that glucagon-like peptide 2 promotes rapid insertion of GLUT2 into the brush-border membrane (8). Moreover, a definitive confirmation of the model has recently been provided by the observation that when the intestine of wild type mice is challenged with sugars by gastric intubation, a large increase in fructose transport occurs within minutes; the increase in transport does not occur in GLUT2-null mice and is attributable entirely to GLUT2 (9).…”

mentioning

confidence: 99%

See 1 more Smart Citation

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

Helliwell

Rumsby

Kellett

2003

Journal of Biological Chemistry

View full text Add to dashboard Cite

Stimulation of intestinal fructose absorption by phorbol 12-myristate 13-acetate (PMA) results from rapid insertion of GLUT2 into the brush-border membrane and correlates with protein kinase C (PKC) ␤II activation. We have therefore investigated the role of phosphatidylinositol 3 (PI3)-kinase and mammalian target of rapamycin in the regulation of fructose absorption by PKC ␤II phosphorylation. In isolated jejunal loops, stimulation of fructose absorption by PMA was inhibited by preperfusion with wortmannin or rapamycin, which blocked GLUT2 activation and insertion into the brushborder membrane. Antibodies to the last 18 and last 10 residues of the C-terminal region of PKC ␤II recognized several species differentially in Western blots. Extensive cleavage of native enzyme (80/78 kDa) to a catalytic domain product of 49 kDa occurred. PMA and sugars provoked turnover and degradation of PKC ␤II by dephosphorylation to a 42-kDa species, which was converted to polyubiquitylated species detected at 180 and 250؉ kDa. PMA increased the level of the PKC ␤II 49-kDa species, which correlates with the GLUT2 level; wortmannin and rapamycin blocked these effects of PMA. Rapamycin and wortmannin inhibited PKC ␤II turnover. PI3-kinase, PDK-1, and protein kinase B were present in the brush-border membrane, where their levels were increased by PMA and blocked by the inhibitors. We conclude that GLUT2-mediated fructose absorption is regulated through PI3-kinase and mammalian target of rapamycin-dependent pathways, which control phosphorylation of PKC ␤II and its substrate-induced turnover and ubiquitin-dependent degradation. These findings suggest possible mechanisms for short term control of intestinal sugar absorption by insulin and amino acids.Intestinal glucose absorption comprises two components (for a review, see Ref. 1). It is well established that one of these is an active component mediated by the Na ϩ /glucose cotransporter, SGLT1. 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).The K a and J max of the facilitated component are 2-and 3-fold, respectively, of those for SGLT1 in vivo. After a meal, the average concentration across the luminal contents of rat jejunum reaches 48 mM (4), close to the K m of the facilitated component, and much higher concentrations may well be present locally at the brush-border membrane, as a result of the hydrolysis of complex dietary sugars (5). The facilitated component therefore appears to provide the major route by which glucose is absorbed immediately after a meal. Moreover, the activation of GLUT2 and its rapid trafficking to...

show abstract

Section: Resultssupporting

confidence: 61%

mentioning

confidence: 99%

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

Helliwell

Rumsby

Kellett

2003

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…It is important to characterize whether GLP2 increases glucose incorporation in adipocytes when their response to insulin is impaired by obesity conditions. In fact, although there are conflicting reports regarding the alterations in the basal glucose uptake, most reports provide evidence that insulin-induced glucose incorporation is suppressed in the obese state (Talior et al 2003, Sancho et al 2006, Crowe et al 2008, and as GLP2 rapidly increases intestinal hexose absorption (Cheeseman 1997, Au et al 2002, it is not unlikely to hypothesize that it contributes to clearance of plasma glucose through an action on adipocytes. In addition or alternatively, GLP2 might influence and modulate the quality and quantity of secreted adipokines and the inflammatory state of adipose tissue.…”

Section: Mechanistic Insightmentioning

confidence: 99%

“…In fact, it induces crypt cell proliferation and inhibition of apoptosis, resulting in an increase of villous height and in the expansion of the absorptive mucosal surface in the small and large intestine (Drucker et al 1996, Tsai et al 1997, Drucker & Yusta 2014. Moreover, GLP2 increases the uptake of sugars by augmenting the activity and the expression of transporters (Cheeseman 1997, Au et al 2002, Ramsanahie et al 2004, Sueyoshi et al 2014 and by enhancing the expression of different enzymes involved in digestion (Brubaker et al 1997a, Petersen et al 2002. Evidence from studies on humans and animal models suggests that GLP2 also plays a role in lipid absorption.…”

Section: Overview On Glp2mentioning

confidence: 99%

GLP2: an underestimated signal for improving glycaemic control and insulin sensitivity

Amato¹,

Baldassano²,

Mulè³

2016

Journal of Endocrinology

View full text Add to dashboard Cite

Glucagon-like peptide 2 (GLP2) is a proglucagon-derived peptide produced by intestinal enteroendocrine L-cells and by a discrete population of neurons in the brainstem, which projects mainly to the hypothalamus. The main biological actions of GLP2 are related to the regulation of energy absorption and maintenance of mucosal morphology, function and integrity of the intestine; however, recent experimental data suggest that GLP2 exerts beneficial effects on glucose metabolism, especially in conditions related to increased uptake of energy, such as obesity, at least in the animal model. Indeed, mice lacking GLP2 receptor selectively in hypothalamic neurons that express proopiomelanocortin show impaired postprandial glucose tolerance and hepatic insulin resistance (by increased gluconeogenesis). Moreover, GLP2 acts as a beneficial factor for glucose metabolism in mice with high-fat diet-induced obesity. Thus, the aim of this review is to update and summarize current knowledge about the role of GLP2 in the control of glucose homeostasis and to discuss how this molecule could exert protective effects against the onset of related obesity type 2 diabetes.

show abstract

“…A high sugar intake is a physiological regulator of this process, increasing monosaccharide uptake threefold in vivo (6). The recruitment of GLUT2 in BBM was also observed in conditions of increased calorie demand and glucagon-like peptide 2 treatment (7)(8)(9)(10)(11).…”

mentioning

confidence: 98%

Insulin Internalizes GLUT2 in the Enterocytes of Healthy but Not Insulin-Resistant Mice

et al. 2008

View full text Add to dashboard Cite

OBJECTIVES-A physiological adaptation to a sugar-rich meal is achieved by increased sugar uptake to match dietary load, resulting from a rapid transient translocation of the fructose/ glucose GLUT2 transporter to the brush border membrane (BBM) of enterocytes. The aim of this study was to define the contributors and physiological mechanisms controlling intestinal sugar absorption, focusing on the action of insulin and the contribution of GLUT2-mediated transport. RESEARCH DESIGN AND METHODS-The studies were performed in the human enterocytic colon carcinoma TC7 subclone (Caco-2/TC7) cells and in vivo during hyperinsulinemiceuglycemic clamp experiments in conscious mice. Chronic highfructose or high-fat diets were used to induce glucose intolerance and insulin resistance in mice. RESULTS AND CONCLUSIONS-InCaco-2/TC7 cells, insulin action diminished the transepithelial transfer of sugar and reduced BBM and basolateral membrane (BLM) GLUT2 levels, demonstrating that insulin can target sugar absorption by controlling the membrane localization of GLUT2 in enterocytes. Similarly, in hyperinsulinemic-euglycemic clamp experiments in sensitive mice, insulin abolished GLUT2 (i.e., the cytochalasin B-sensitive component of fructose absorption), decreased BBM GLUT2, and concomitantly increased intracellular GLUT2. Acute insulin treatment before sugar intake prevented the insertion of GLUT2 into the BBM. Insulin resistance in mice provoked a loss of GLUT2 trafficking, and GLUT2 levels remained permanently high in the BBM and low in the BLM. We propose that, in addition to its peripheral effects, insulin inhibits intestinal sugar absorption to prevent excessive blood glucose excursion after a sugar meal. This protective mechanism is lost in the insulin-resistant state induced by high-fat or high-fructose feeding. Diabetes 57: 555-562, 2008 I ntestinal sugar transport constantly adapts to the dietary environment. At low levels, the end products of carbohydrate digestion are absorbed by a twostep membrane-transport process involving the sodium-dependent glucose cotransporter (SGLT1) and the facilitative fructose transporter (GLUT5) in the brush border membrane (BBM) (1) lining the lumen. GLUT2 in the basolateral membrane (BLM) (2) ensures sugar exit into the blood stream (3). The level of sugar absorption is also regulated by a rapid and transient recruitment of GLUT2 into enterocyte BBM (4,5). A high sugar intake is a physiological regulator of this process, increasing monosaccharide uptake threefold in vivo (6). The recruitment of GLUT2 in BBM was also observed in conditions of increased calorie demand and glucagon-like peptide 2 treatment (7-11).The mechanisms by which GLUT2 leaves the BBM in the absence of luminal sugar (interprandial periods) are unknown. Of the possible physiological stimuli occurring during feeding, insulin was thought to be a candidate because it exerts systemic hypoglycemic effects by stimulating the translocation of GLUT4 into the plasma membrane of skeletal muscle and adipose cells (rev. in 12) and d...

show abstract

Rapid insertion of GLUT2 into the rat jejunal brush-border membrane promoted by glucagon-like peptide 2

Cited by 155 publications

References 27 publications

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

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

GLP2: an underestimated signal for improving glycaemic control and insulin sensitivity

Insulin Internalizes GLUT2 in the Enterocytes of Healthy but Not Insulin-Resistant Mice

Contact Info

Product

Resources

About