SLC2A2 mutations can cause neonatal diabetes, suggesting GLUT2 may have a role in human insulin secretion

详细信息    查看全文

• 作者：F. H. Sansbury (12)
  S. E. Flanagan (1)
  J. A. L. Houghton (12)
  F. L. Shuixian Shen (3)
  A. M. S. Al-Senani (4)
  A. M. Habeb (5)
  M. Abdullah (6)
  A. Kariminejad (7)
  S. Ellard (12)
  A. T. Hattersley (12) andrew.hattersley@pms.ac.uk
• 关键词：Fanconi– ; Bickel syndrome – ; FBS – ; GLUT2 – ; Neonatal diabetes mellitus – ; Permanent neonatal diabetes mellitus – ; PNDM – ; SLC2A2 – ; TNDM – ; Transient neonatal diabetes mellitus
• 刊名：Diabetologia
• 出版年：2012
• 出版时间：September 2012
• 年：2012
• 卷：55
• 期：9
• 页码：2381-2385
• 全文大小：120.2 KB
• 参考文献：1. Thorens B, Cheng Z-Q, Brown DF, Lodish HF (1990) Liver glucose transporter: a basolateral protein in hepatocytes and intestine and kidney cells. Am J Physiol 259(Cell Physiol 28):C279–C285
  2. Guillam M-T, H眉mmler E, Schaerer E et al (1997) Early diabetes and abnormal postnatal pancreatic islet development in mice lacking Glut-2. Nat Genet 17:327–330
  3. Guillam M-T, Dupraz P, Thorens B (2000) Glucose uptake, utilization, and signaling in GLUT2-null islets. Diabetes 49:1485–1491
  4. De Vos A, Heimberg H, Quartier E et al (1995) Human and rat beta cells differ in glucose transporter but not in glucokinase gene expression. J Clin Invest 96:2489–2495
  5. Richardson CC, Hussain K, Jones PM et al (2007) Low levels of glucose transporters and K+ ATP channels in human pancreatic beta cells early in development. Diabetologia 50:1000–1005
  6. McCulloch LJ, van de Bunt M, Braun M, Frayn KN, Clark A, Gloyn AL (2011) GLUT2 (SLC2A2) is not the principal glucose transporter in human pancreatic beta cells: Implications for understanding genetic association signals at this locus. Mol Genet Metab 104:648
  7. Santer R, Schneppenheim R, Dombrowski A, G枚tze H, Steinmann B, Schaub J (1997) Mutations in GLUT2, the gene for the liver-type glucose transporter, in patients with Fanconi-Bickel syndrome. Nat Genet 17:324–326
  8. Santer R, Steinmann B, Schaub J (2002) Fanconi-Bickel syndrome—a congenital defect of facilitative glucose transport. Curr Mol Med 2:213–227
  9. Murphy R, Ellard S, Hattersley AT (2008) Clinical implications of a molecular genetic classification of monogenic beta-cell diabetes. Nat Clin Pract Endocrinol Metab 4:200–213
  10. Yoo H-W, Shin Y-L, Seo E-J, Kim G-H (2002) Identification of a novel mutation in the GLUT2 gene in a patient with Fanconi-Bickel syndrome presenting with neonatal diabetes mellitus and galactosaemia. Eur J Pediatr 161:351–353
  11. Habeb AM, Al-Magamsi MSF, Eid IM et al (2011) Incidence, genetics, and clinical phenotype of permanent neonatal diabetes mellitus in northwest Saudi Arabia. Pediatr Diabetes. doi:10.1111/j.1399-5448.2011.00828.x
  12. Manz F, Bickel H, Brodehl J et al (1987) Fanconi-Bickel syndrome. Pediatr Nephrol 1:509–518
  13. Garty R, Cooper M, Tabachnik E (1974) The Fanconi syndrome associated with hepatic glycogenosis and abnormal metabolism of galactose. J Pediatr 85:821–823
  14. Chesney RW, Kaplan BS, Colle E et al (1980) Abnormalities of carbohydrate metabolism in idiopathic Fanconi syndrome. Pediatr Res 14:209–215
  15. Taha D, Al-Harbi N, Al-Sabban E (2008) Hyperglycemia and hypoinsulinemia in patients with Fanconi–Bickel syndrome. J Pediatr Endocrinol Metab 21:581–586
  16. De Vivo DC, Trifiletti RR, Jacobson RI, Ronen GM, Behmand RA, Harik SI (1991) Defective glucose transport across the blood–brain barrier as a cause of hypoglycorrhachia, seizures and developmental delay. N Engl J Med 325:703
  17. Seidner G, Alvarez MG, Yeh J-I et al (1998) GLUT-1 deficiency syndrome caused by haploinsufficiency of the blood–brain barrier hexose carrier. Nat Genet 18:188–191
  18. Baroni MG, Sentinelli F, Massa O (2001) Single-strand conformation polymorphism analysis of the glucose transporter gene GLUT1 in maturity-onset diabetes of the young. J Mol Med 79:270–274
  19. Whitesell RR, Powers AC, Regen DM, Abumrad NA (1991) Transport and metabolism of glucose in an insulin-secreting cell line, beta TC-1. Biochemistry 30:11560–11566
  20. MacDonald PE, Joseph JW, Rorsman P (2005) Glucose-sensing mechanisms in pancreatic beta-cells. Phil Trans R Soc B 360:2211
  21. Leturque A, Brot-Laroche E, Le Gall M (2009) GLUT2 mutations, translocation, and receptor function in diet sugar managing. Am J Physiol Endocrinol Metab 296:E985–E992
  22. Hughes SD, Quaade C, Johnson JH, Ferber S, Newgard CB (1993) Transfection of AtT-20ins cells with GLUT-2 but not GLUT-1 confers glucose-stimulated insulin secretion. J Biol Chem 268:15205–15212
  23. Brown GK (2000) Glucose transporters: structure, function and consequences of deficiency. J Inherit Metab Dis 23:237–246
  24. Dupuis J, Langenberg C, Prokopenko I et al (2010) New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk. Nat Genet 42:105–116
  25. Ingelsson E, Langenberg C, Hivert MF et al (2010) Detailed physiologic characterization reveals diverse mechanisms for novel genetic loci regulating glucose and insulin metabolism in humans. Diabetes 59:1266–1275
• 作者单位：1. Peninsula College of Medicine and Dentistry, University of Exeter, Peninsula Medical School Building, Barrack Road, Exeter, Devon EX2 5DW, UK2. Royal Devon & Exeter NHS Foundation Trust, Barrack Road, Exeter, Devon EX2 5DW, UK3. Children鈥檚 Hospital of Fudan University, Shanghai, People鈥檚 Republic of China4. Royal Hospital, Muscat, Oman5. Maternity and Children Hospital, Al-Madinah, Kingdom of Saudi Arabia6. Department of Paediatrics, Faculty of Medicine, University of Khartoum, Khartoum, Sudan7. Kariminejad-Najmabadi Pathology and Genetics Center, Tehran, Iran
• ISSN：1432-0428

文摘

Aims The gene SLC2A2 encodes GLUT2, which is found predominantly in pancreas, liver, kidney and intestine. In mice, GLUT2 is the major glucose transporter into pancreatic beta cells, and biallelic Slc2a2 inactivation causes lethal neonatal diabetes. The role of GLUT2 in human beta cells is controversial, and biallelic SLC2A2 mutations cause Fanconi–Bickel syndrome (FBS), with diabetes rarely reported. We investigated the potential role of GLUT2 in the neonatal period by testing whether SLC2A2 mutations can present with neonatal diabetes before the clinical features of FBS appear.