LOSS OF GLUT2 GLUCOSE-TRANSPORTER EXPRESSION IN PANCREATIC BETA-CELLSFROM DIABETIC CHINESE-HAMSTERS

The diabetic Chinese hamster is a well-established animal model for NI DDM with a defective glucose-induced insulin secretory response. In th e pancreas of nondiabetic hamsters, the GLUT2 glucose transporter was localized in the plasma membrane of insulin-positive beta cells. At va riance with the rat, immunoreactivity was also detected in the cytopla sm. Other islet cell types were not GLUT2 positive. GLUT2 immunoreacti vity was already significantly reduced in beta cells from mildly diabe tic animals in spite of a normal insulin immunoreactivity. In severely diabetic animals the majority of the beta cells had lost GLUT2 immuno staining. This observation was confirmed in a Western blot analysis of the GLUT2 protein in isolated pancreatic islets. Only beta cells that were densely immunostained for insulin were still GLUT2 positive. How ever, around 40% of the beta cells devoid of GLUT:! immunoreactivity w ere still insulin immunoreactive. Thus, the loss of GLUT2 immunoreacti vity, which is an important component of the glucose recognition appar atus of the pancreatic beta cell, is an early indicator of beta cell d ysfunction before the development of degenerative lesions or the loss of insulin immunoreactivity. GLUT2 loss may be important in the deteri oration of glucose-induced insulin secretion in the diabetic Chinese h amster.