The loss of GLUT2 expression in the pancreatic beta-cells of diabetic db/db mice is associated with an impaired DNA-binding activity of islet-specific trans-acting factors

Mol Cell Endocrinol. 1997 Nov 30;135(1):59-65. doi: 10.1016/s0303-7207(97)00190-1.


GLUT2 expression is reduced in the pancreatic beta-cells of several diabetic animals. The transcriptional control of the gene in beta-cells involves at least two islet-specific DNA-binding proteins, GTIIa and PDX-1, which also transactivates the insulin, somatostatin and glucokinase genes. In this report, we assessed the DNA-binding activities of GTIIa and PDX-1 to their respective cis-elements of the GLUT2 promoter using nuclear extracts prepared from pancreatic islets of 12 week old db/db diabetic mice. We show that the decreased GLUT2 mRNA expression correlates with a decrease of the GTIIa DNA-binding activity, whereas the PDX-1 binding activity is increased. In these diabetic animals, insulin mRNA expression remains normal. The adjunction of dexamethasone to isolated pancreatic islets, a treatment previously shown to decrease PDX-1 expression in the insulin-secreting HIT-T15 cells, has no effect on the GTIIa and PDX-1 DNA-binding activities. These data suggest that the decreased activity of GTIIa, in contrast to PDX-1, may be a major initial step in the development of the beta-cell dysfunction in this model of diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • DNA / metabolism*
  • Diabetes Mellitus / metabolism*
  • Gene Expression*
  • Glucose Transporter Type 2
  • Homeodomain Proteins*
  • Insulin / genetics
  • Islets of Langerhans / metabolism*
  • Male
  • Mice
  • Monosaccharide Transport Proteins / genetics*
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Trans-Activators / metabolism*


  • Glucose Transporter Type 2
  • Homeodomain Proteins
  • Insulin
  • Monosaccharide Transport Proteins
  • RNA, Messenger
  • Trans-Activators
  • pancreatic and duodenal homeobox 1 protein
  • DNA