glucose transporter type 2

Summary

Summary: A glucose transport facilitator that is expressed primarily in PANCREATIC BETA CELLS; LIVER; and KIDNEYS. It may function as a GLUCOSE sensor to regulate INSULIN release and glucose HOMEOSTASIS.

Top Publications

  1. Iñigo C, Patel N, Kellett G, Barber A, Lostao M. Luminal leptin inhibits intestinal sugar absorption in vivo. Acta Physiol (Oxf). 2007;190:303-10 pubmed
    ..These observations support the view that gastric leptin exerts a regulatory role on intestinal sugar absorption in the postprandial state by modifying the active component of absorption. ..
  2. Leturque A, Brot Laroche E, Le Gall M. GLUT2 mutations, translocation, and receptor function in diet sugar managing. Am J Physiol Endocrinol Metab. 2009;296:E985-92 pubmed publisher
    ..These recent developments are examined here in heath and metabolic disease, highlighting various unanswered questions. ..
  3. Zheng Y, Scow J, Duenes J, Sarr M. Mechanisms of glucose uptake in intestinal cell lines: role of GLUT2. Surgery. 2012;151:13-25 pubmed publisher
    ..IEC-6 cells do not appear to express functional GLUT2. ..
  4. Laukkanen O, Lindström J, Eriksson J, Valle T, Hämäläinen H, Ilanne Parikka P, et al. Polymorphisms in the SLC2A2 (GLUT2) gene are associated with the conversion from impaired glucose tolerance to type 2 diabetes: the Finnish Diabetes Prevention Study. Diabetes. 2005;54:2256-60 pubmed
    ..56 [1.78-17.39], P = 0.003) but not in the intervention group. We conclude that the SNPs of SLC2A2 predict the conversion to diabetes in obese subjects with IGT. ..
  5. Barroso I, Luan J, Middelberg R, Harding A, Franks P, Jakes R, et al. Candidate gene association study in type 2 diabetes indicates a role for genes involved in beta-cell function as well as insulin action. PLoS Biol. 2003;1:E20 pubmed
    ..The absence of large single-gene effects and the detection of multiple small effects accentuate the need for the study of larger populations in order to reliably identify the size of effect we now expect for complex diseases...
  6. Helliwell P, Rumsby M, Kellett G. Intestinal sugar absorption is regulated by phosphorylation and turnover of protein kinase C betaII mediated by phosphatidylinositol 3-kinase- and mammalian target of rapamycin-dependent pathways. J Biol Chem. 2003;278:28644-50 pubmed
    ..These findings suggest possible mechanisms for short term control of intestinal sugar absorption by insulin and amino acids. ..
  7. Yajima K, Hirose H, Fujita H, Seto Y, Fujita H, Ukeda K, et al. Combination therapy with PPARgamma and PPARalpha agonists increases glucose-stimulated insulin secretion in db/db mice. Am J Physiol Endocrinol Metab. 2003;284:E966-71 pubmed
    ..GSIS was further increased by PPARgamma and -alpha agonists. We conclude that combination therapy with PPARgamma and PPARalpha agonists may be more useful with respect to body weight and pancreatic GSIS in type 2 diabetes with obesity. ..
  8. Kilpeläinen T, Lakka T, Laaksonen D, Laukkanen O, Lindstrom J, Eriksson J, et al. Physical activity modifies the effect of SNPs in the SLC2A2 (GLUT2) and ABCC8 (SUR1) genes on the risk of developing type 2 diabetes. Physiol Genomics. 2007;31:264-72 pubmed
    ..022-0.027 for the SNPs in SLC2A2, and P = 0.007 for rs3758947). We conclude that moderate-to-vigorous PA may modify the risk of developing T2D associated with genes regulating insulin secretion (SLC2A2, ABCC8) in persons with IGT...
  9. Eny K, Wolever T, Fontaine Bisson B, El Sohemy A. Genetic variant in the glucose transporter type 2 is associated with higher intakes of sugars in two distinct populations. Physiol Genomics. 2008;33:355-60 pubmed publisher
    ..b>Glucose transporter type 2 (GLUT2)-null mice fail to control their food intake in response to glucose, suggesting a potential role ..

More Information

Publications62

  1. Souza M, Machado U, Okamoto M, Bertoluci M, Ponpermeyer C, Leguisamo N, et al. Reduced cortical renal GLUT1 expression induced by angiotensin-converting enzyme inhibition in diabetic spontaneously hypertensive rats. Braz J Med Biol Res. 2008;41:960-8 pubmed
    ..In conclusion, ramipril is effective in lowering renal tissue angiotensin-converting enzyme activity, as well as blocking cortical GLUT1 overexpression, which may be beneficial in arresting the development of diabetic nephropathy. ..
  2. Evans Molina C, ROBBINS R, Kono T, Tersey S, Vestermark G, Nunemaker C, et al. Peroxisome proliferator-activated receptor gamma activation restores islet function in diabetic mice through reduction of endoplasmic reticulum stress and maintenance of euchromatin structure. Mol Cell Biol. 2009;29:2053-67 pubmed publisher
    ..We conclude that PPAR-gamma agonists exert a direct effect in diabetic islets to reduce endoplasmic reticulum stress and enhance Pdx1 levels, leading to favorable alterations of the islet gene chromatin architecture...
  3. Cantley J, Selman C, Shukla D, Abramov A, Forstreuter F, Esteban M, et al. Deletion of the von Hippel-Lindau gene in pancreatic beta cells impairs glucose homeostasis in mice. J Clin Invest. 2009;119:125-35 pubmed publisher
    ..These data suggest that VHL/HIF oxygen-sensing mechanisms play a critical role in glucose homeostasis and that activation of this pathway in response to decreased islet oxygenation may contribute to beta cell dysfunction. ..
  4. Zhang X, Sun N, Wang L, Guo H, Guan Q, Cui B, et al. AMP-activated protein kinase and pancreatic/duodenal homeobox-1 involved in insulin secretion under high leucine exposure in rat insulinoma beta-cells. J Cell Mol Med. 2009;13:758-70 pubmed publisher
    ..The study indicated that chronic leucine might result in an increase in AMPK and then a decrease in PDX-l, in turn to depress GCK and GLUT2 resulting in decreased GSIS at high glucose and insulin content. ..
  5. Stolarczyk E, Guissard C, Michau A, Even P, Grosfeld A, Serradas P, et al. Detection of extracellular glucose by GLUT2 contributes to hypothalamic control of food intake. Am J Physiol Endocrinol Metab. 2010;298:E1078-87 pubmed publisher
  6. Marty N, Dallaporta M, Foretz M, Emery M, Tarussio D, Bady I, et al. Regulation of glucagon secretion by glucose transporter type 2 (glut2) and astrocyte-dependent glucose sensors. J Clin Invest. 2005;115:3545-53 pubmed
    Ripglut1;glut2-/- mice have no endogenous glucose transporter type 2 (glut2) gene expression but rescue glucose-regulated insulin secretion...
  7. Dai C, Huh C, Thorgeirsson S, Liu Y. Beta-cell-specific ablation of the hepatocyte growth factor receptor results in reduced islet size, impaired insulin secretion, and glucose intolerance. Am J Pathol. 2005;167:429-36 pubmed
    ..Therefore, HGF/c-met signaling plays an imperative role in controlling islet growth, in regulating beta-cell function, and in maintaining glucose homeostasis. ..
  8. Bady I, Marty N, Dallaporta M, Emery M, Gyger J, Tarussio D, et al. Evidence from glut2-null mice that glucose is a critical physiological regulator of feeding. Diabetes. 2006;55:988-95 pubmed
    ..Furthermore, inactivation of these glucose sensors causes overeating. ..
  9. Im S, Kim J, Kim T, Song X, Kim S, Kim H, et al. Identification and characterization of peroxisome proliferator response element in the mouse GLUT2 promoter. Exp Mol Med. 2005;37:101-10 pubmed
    ..Taken together, liver GLUT2 may be a direct target of PPAR-gamma ligand contributing to glucose transport into liver in a condition when PAPR-gamma expression is increased as in type 2 diabetes or in severe obesity. ..
  10. Eisenberg M, Maker A, Slezak L, Nathan J, Sritharan K, Jena B, et al. Insulin receptor (IR) and glucose transporter 2 (GLUT2) proteins form a complex on the rat hepatocyte membrane. Cell Physiol Biochem. 2005;15:51-8 pubmed
    ..Fluorescence-resonance energy transfer studies further confirmed this association. We conclude that IR and GLUT2 form a receptor-transporter complex in hepatocytes, which forms a mechanism of insulin-mediated hepatic glucose regulation. ..
  11. Kim H, Noh J, Hong S, Hwang Y, Yang T, Lee M, et al. Rosiglitazone stimulates the release and synthesis of insulin by enhancing GLUT-2, glucokinase and BETA2/NeuroD expression. Biochem Biophys Res Commun. 2008;367:623-9 pubmed publisher
    ..These results suggest that RGZ could stimulate the release and synthesis of insulin through the upregulation of GLUT-2, GCK, and BETA2/NeuroD gene expression. ..
  12. Mace O, Lister N, Morgan E, Shepherd E, Affleck J, Helliwell P, et al. An energy supply network of nutrient absorption coordinated by calcium and T1R taste receptors in rat small intestine. J Physiol. 2009;587:195-210 pubmed publisher
    ..The network may control energy supply. ..
  13. Iqbal C, Qandeel H, Zheng Y, Duenes J, Sarr M. Mechanisms of ileal adaptation for glucose absorption after proximal-based small bowel resection. J Gastrointest Surg. 2008;12:1854-64; discussion 1864-5 pubmed publisher
    ..04 each) correlating with change in villus height (p < or = 0.03). Ileal adaptation for glucose transport occurs through cellular proliferation (hyperplasia) and not through cellular upregulation of glucose transporters. ..
  14. Kellett G, Brot Laroche E, Mace O, Leturque A. Sugar absorption in the intestine: the role of GLUT2. Annu Rev Nutr. 2008;28:35-54 pubmed publisher
    ..evidence, however, indicates that the diffusive component is mediated by the transient insertion of glucose transporter type 2 (GLUT2) into the apical membrane...
  15. Gouyon F, Caillaud L, Carriere V, Klein C, Dalet V, Citadelle D, et al. Simple-sugar meals target GLUT2 at enterocyte apical membranes to improve sugar absorption: a study in GLUT2-null mice. J Physiol. 2003;552:823-32 pubmed
    ..Thus, GLUT2 and GLUT5 could exert complementary roles in adapting the absorption capacity of the intestine to occasional or repeated loads of dietary sugars. ..
  16. Roncero I, Alvarez E, Chowen J, Sanz C, Rabano A, Vazquez P, et al. Expression of glucose transporter isoform GLUT-2 and glucokinase genes in human brain. J Neurochem. 2004;88:1203-10 pubmed
  17. Walker J, Jijon H, Diaz H, Salehi P, Churchill T, Madsen K. 5-aminoimidazole-4-carboxamide riboside (AICAR) enhances GLUT2-dependent jejunal glucose transport: a possible role for AMPK. Biochem J. 2005;385:485-91 pubmed
    ..We conclude that the activation of AMPK results in an up-regulation of non-energy requiring glucose uptake by GLUT2 and a concurrent down-regulation of sodium-dependent glucose transport. ..
  18. Artner I, Blanchi B, Raum J, Guo M, Kaneko T, Cordes S, et al. MafB is required for islet beta cell maturation. Proc Natl Acad Sci U S A. 2007;104:3853-8 pubmed
    ..These results demonstrate that MafB plays a previously uncharacterized role by regulating transcription of key factors during development that are required for the production of mature alpha and beta cells. ..
  19. Schaan B, Irigoyen M, Bertoluci M, Lima N, Passaglia J, Hermes E, et al. Increased urinary TGF-beta1 and cortical renal GLUT1 and GLUT2 levels: additive effects of hypertension and diabetes. Nephron Physiol. 2005;100:p43-50 pubmed
    ..The impact on urinary TGF-beta1 occurs when diabetes and hypertension are associated, suggesting an effect that is triggered in the presence of GLUT1 overexpression and hyperglycemia. ..
  20. Habold C, Foltzer Jourdainne C, Le Maho Y, Lignot J, Oudart H. Intestinal gluconeogenesis and glucose transport according to body fuel availability in rats. J Physiol. 2005;566:575-86 pubmed
    ..Finally, refeeding triggered GLUT2 and GLUT5 synthesis and apical recruitment of GLUT2, to absorb larger amounts of hexoses. ..
  21. Im S, Kim S, Kim H, Ahn Y. Transcriptional regulation of glucose sensors in pancreatic beta cells and liver. Curr Diabetes Rev. 2006;2:11-8 pubmed
    ..Here, we review recent progress in elucidating the transcriptional regulation of glucose sensors in the liver and pancreatic beta-cells and the relevance to T2DM. ..
  22. Berry G, Baynes J, Wells Knecht K, Szwergold B, Santer R. Elements of diabetic nephropathy in a patient with GLUT 2 deficiency. Mol Genet Metab. 2005;86:473-7 pubmed
    ..Elevated levels of glucose and/or its metabolites in renal tubular cells may be necessary but not sufficient for the development of both the renal tubulopathy and diabetic-like glomerular disease in GLUT2 deficiency. ..
  23. Marks J, Carvou N, Debnam E, Srai S, Unwin R. Diabetes increases facilitative glucose uptake and GLUT2 expression at the rat proximal tubule brush border membrane. J Physiol. 2003;553:137-45 pubmed
    ..Our findings indicate that streptozotocin-induced diabetes causes the insertion of GLUT2 into the BBM and this may provide a low affinity/high capacity route of entry into proximal tubule cells during hyperglycaemia. ..
  24. Zeuthen T, Zeuthen E, MacAulay N. Water transport by GLUT2 expressed in Xenopus laevis oocytes. J Physiol. 2007;579:345-61 pubmed
    ..This capacity for cotransport is 10 times smaller than that of the Na(+)-coupled glucose transporters (SGLT1). The physiological role of GLUT2 for intestinal transport under conditions of high luminal sugar concentrations is discussed. ..
  25. Freitas H, Schaan B, David Silva A, Sabino Silva R, Okamoto M, Alves Wagner A, et al. SLC2A2 gene expression in kidney of diabetic rats is regulated by HNF-1alpha and HNF-3beta. Mol Cell Endocrinol. 2009;305:63-70 pubmed publisher
    ..Furthermore, recovery of SLC2A2 gene after 6-day insulin treatment also involves HNF-1alpha and HNF-3beta activity. ..
  26. Im S, Kang S, Kim S, Kim H, Kim J, Kim K, et al. Glucose-stimulated upregulation of GLUT2 gene is mediated by sterol response element-binding protein-1c in the hepatocytes. Diabetes. 2005;54:1684-91 pubmed
    ..These results indicate that SREBP-1c mediates glucose-stimulated GLUT2 gene expression in hepatocytes. ..
  27. Ueda T, Furusawa T, Kurahashi T, Tessarollo L, Bustin M. The nucleosome binding protein HMGN3 modulates the transcription profile of pancreatic beta cells and affects insulin secretion. Mol Cell Biol. 2009;29:5264-76 pubmed publisher
    ..Our results identify a new regulator of glucose homeostasis and demonstrate a link between the activity of a nucleosome binding structural protein and the regulation of insulin secretion. ..
  28. Gagnon M, Bissonnette P, Deslandes L, Wallendorff B, Lapointe J. Glucose accumulation can account for the initial water flux triggered by Na+/glucose cotransport. Biophys J. 2004;86:125-33 pubmed
  29. Schaan B, Irigoyen M, Lacchini S, Moreira E, Schmid H, Machado U. Sympathetic modulation of the renal glucose transporter GLUT2 in diabetic rats. Auton Neurosci. 2005;117:54-61 pubmed
  30. Kwon O, Eck P, Chen S, Corpe C, Lee J, Kruhlak M, et al. Inhibition of the intestinal glucose transporter GLUT2 by flavonoids. FASEB J. 2007;21:366-77 pubmed
  31. Freitas H, D Agord Schaan B, da Silva R, Okamoto M, Oliveira Souza M, Machado U. Insulin but not phlorizin treatment induces a transient increase in GLUT2 gene expression in the kidney of diabetic rats. Nephron Physiol. 2007;105:p42-51 pubmed
    ..The 6-day normalization of GLUT2, however, was induced by both insulin and phlorizin treatment, which seems to be related to the plasma glucose lowering. ..
  32. Tobin V, Le Gall M, Fioramonti X, Stolarczyk E, Blazquez A, Klein C, et al. Insulin internalizes GLUT2 in the enterocytes of healthy but not insulin-resistant mice. Diabetes. 2008;57:555-62 pubmed
    ..This protective mechanism is lost in the insulin-resistant state induced by high-fat or high-fructose feeding. ..
  33. Igl W, Johansson A, Wilson J, Wild S, Polasek O, Hayward C, et al. Modeling of environmental effects in genome-wide association studies identifies SLC2A2 and HP as novel loci influencing serum cholesterol levels. PLoS Genet. 2010;6:e1000798 pubmed publisher
    ..6 x 10(-5), p(SE,adjusted) = 2.2 x 10(-6), p(NS,unadjusted) = 0.047) in the SLC2A2 (Glucose transporter type 2) and rs2000999 (p(SE,unadjusted) = 1.1 x 10(-3), p(SE,adjusted) = 3.8 x 10(-4), p(NS,unadjusted) = 0...
  34. Hou J, Williams D, Vicogne J, Pessin J. The glucose transporter 2 undergoes plasma membrane endocytosis and lysosomal degradation in a secretagogue-dependent manner. Endocrinology. 2009;150:4056-64 pubmed publisher
    ..Together, these data demonstrate that hyperglycemia directly affects beta-cell function and activates a trafficking pathway that results in the rapid endocytosis and degradation of the cell surface GLUT2 glucose transporter. ..
  35. Ohtsubo K, Takamatsu S, Minowa M, Yoshida A, Takeuchi M, Marth J. Dietary and genetic control of glucose transporter 2 glycosylation promotes insulin secretion in suppressing diabetes. Cell. 2005;123:1307-21 pubmed
    ..We infer that beta cell glucose-transporter glycosylation mediates a link between diet and insulin production that typically suppresses the pathogenesis of type 2 diabetes. ..
  36. Affleck J, Helliwell P, Kellett G. Immunocytochemical detection of GLUT2 at the rat intestinal brush-border membrane. J Histochem Cytochem. 2003;51:1567-74 pubmed
    ..The functional and immunocytochemical data are now reconciled. ..
  37. Reimer M, Ahren B. Altered beta-cell distribution of pdx-1 and GLUT-2 after a short-term challenge with a high-fat diet in C57BL/6J mice. Diabetes. 2002;51 Suppl 1:S138-43 pubmed
    ..The mechanisms compromising this beta-cell trafficking remain to be established. ..
  38. Waeber G, Thompson N, Nicod P, Bonny C. Transcriptional activation of the GLUT2 gene by the IPF-1/STF-1/IDX-1 homeobox factor. Mol Endocrinol. 1996;10:1327-34 pubmed
    ..As the glucose transporter type 2 (GLUT2) gene expression is selectively decreased in the beta-pancreatic cells of experimental models of ..
  39. Santer R, Schneppenheim R, Suter D, Schaub J, Steinmann B. Fanconi-Bickel syndrome--the original patient and his natural history, historical steps leading to the primary defect, and a review of the literature. Eur J Pediatr. 1998;157:783-97 pubmed
  40. Ahn Y, Kim J, Han G, Lee B, Kim Y. Cloning and characterization of rat pancreatic beta-cell/liver type glucose transporter gene: a unique exon/intron organization. Arch Biochem Biophys. 1995;323:387-96 pubmed
    ..The region containing -4542/+240 showed the highest CAT activity and further deletion of the region showed gradual decrease in CAT activity. ..
  41. Waeber G, Thompson N, Haefliger J, Nicod P. Characterization of the murine high Km glucose transporter GLUT2 gene and its transcriptional regulation by glucose in a differentiated insulin-secreting cell line. J Biol Chem. 1994;269:26912-9 pubmed
    ..Comparison of the mouse and human promoter regions revealed sequence identity restricted to a few stretches of sequences which suggests that the glucose responsive element(s) may be conserved in these common sequences. ..
  42. Ahlgren U, Jonsson J, Jonsson L, Simu K, Edlund H. beta-cell-specific inactivation of the mouse Ipf1/Pdx1 gene results in loss of the beta-cell phenotype and maturity onset diabetes. Genes Dev. 1998;12:1763-8 pubmed
  43. Thorens B. GLUT2 in pancreatic and extra-pancreatic gluco-detection (review). Mol Membr Biol. 2001;18:265-73 pubmed
    ..These studies may pave the way to a fine dissection of the molecular and cellular components of extra-pancreatic glucose sensors involved in the control of glucose and energy homeostasis. ..
  44. Dyer J, Wood I, Palejwala A, Ellis A, Shirazi Beechey S. Expression of monosaccharide transporters in intestine of diabetic humans. Am J Physiol Gastrointest Liver Physiol. 2002;282:G241-8 pubmed
  45. Guillemain G, Munoz Alonso M, Cassany A, Loizeau M, Faussat A, Burnol A, et al. Karyopherin alpha2: a control step of glucose-sensitive gene expression in hepatic cells. Biochem J. 2002;364:201-9 pubmed
    ..The transitory tethering of karyopherin alpha2 to GLUT2 at the plasma membrane might indicate that the receptor can load the cargo to be imported locally. ..
  46. Au A, Gupta A, Schembri P, Cheeseman C. Rapid insertion of GLUT2 into the rat jejunal brush-border membrane promoted by glucagon-like peptide 2. Biochem J. 2002;367:247-54 pubmed
    ..These results indicate that vascular GLP-2 can promote the insertion of GLUT2 into the rat jejunal BBM providing a low-affinity/high-capacity route of entry for dietary hexoses. ..
  47. Guillam M, Dupraz P, Thorens B. Glucose uptake, utilization, and signaling in GLUT2-null islets. Diabetes. 2000;49:1485-91 pubmed
    ..These data further demonstrate the key role of GLUT2 in murine beta-cells for glucose signaling to insulin secretion and biosynthesis. ..
  48. Kellett G. The facilitated component of intestinal glucose absorption. J Physiol. 2001;531:585-95 pubmed
  49. Shen W, Scearce L, Brestelli J, Sund N, Kaestner K. Foxa3 (hepatocyte nuclear factor 3gamma ) is required for the regulation of hepatic GLUT2 expression and the maintenance of glucose homeostasis during a prolonged fast. J Biol Chem. 2001;276:42812-7 pubmed
    ..In addition, we investigated the hepatic transcription factor network in Foxa3(-/-) mice and found that the normal activation of HNF-4alpha, HNF-1alpha, and PGC-1 induced by fasting is attenuated in mice lacking Foxa3. ..
  50. Gremlich S, Bonny C, Waeber G, Thorens B. Fatty acids decrease IDX-1 expression in rat pancreatic islets and reduce GLUT2, glucokinase, insulin, and somatostatin levels. J Biol Chem. 1997;272:30261-9 pubmed
    ..Fatty acids thus have pleiotropic effects on pancreatic islet gene expression, and the negative control of Idx-1 expression may be an initial event in the development of these multiple defects. ..
  51. Guillam M, Hummler E, Schaerer E, Yeh J, Birnbaum M, Beermann F, et al. Early diabetes and abnormal postnatal pancreatic islet development in mice lacking Glut-2. Nat Genet. 1997;17:327-30 pubmed
    ..Glut-2 is thus required to maintain normal glucose homeostasis and normal function and development of the endocrine pancreas. Its absence leads to symptoms characteristic of non-insulin-dependent diabetes mellitus. ..
  52. Offield M, Jetton T, Labosky P, Ray M, Stein R, Magnuson M, et al. PDX-1 is required for pancreatic outgrowth and differentiation of the rostral duodenum. Development. 1996;122:983-95 pubmed
    ..These results offer additional insight into the role of pdx-1 in the determination and differentiation of the posterior foregut, particularly regarding the proliferation and differentiation of the pancreatic progenitors. ..
  53. Mueckler M, Kruse M, Strube M, Riggs A, Chiu K, Permutt M. A mutation in the Glut2 glucose transporter gene of a diabetic patient abolishes transport activity. J Biol Chem. 1994;269:17765-7 pubmed
    ..The presence of this mutation in a diabetic patient suggests that defects in Glut2 expression may be causally involved in the pathogenesis of non-insulin-dependent diabetes. ..