Virchows Arch (1996) 428:177-185 © Springer-Verlag 1996 Anne Ji~rns • Markus Tiedge • Eckart Sickel Sigurd Lenzen Loss of GLUT2 glucose transporter expression in pancreatic beta cells from diabetic Chinese hamsters Received: 25 January 1996 / Accepted: 4 March 1996 Abstract The diabetic Chinese hamster is a well-estab- lished animal model for NIDDM with a defective glu- cose-induced insulin secretory response. In the pancreas of nondiabetic hamsters, the GLUT2 glucose transporter was localized in the plasma membrane of insulin-posi- tive beta cells. At variance with the rat, immunoreactivi- ty was also detected in the cytoplasm. Other islet cell types were not GLUT2 positive. GLUT2 immunoreactiv- ity was already significantly reduced in beta cells from mildly diabetic animals in spite of a normal insulin im- munoreactivity. In severely diabetic animals the majority of the beta cells had lost GLUT2 immunostaining. This observation was confirmed in a Western blot analysis of the GLUT2 protein in isolated pancreatic islets. Only be- ta cells that were densely immunostained for insulin were still GLUT2 positive. However, around 40% of the beta cells devoid of GLUT2 immunoreactivity were still insulin immunoreactive. Thus, the loss of GLUT2 immu- noreactivity, which is an important component of the glucose recognition apparatus of the pancreatic beta cell, is an early indicator of beta cell dysfunction before the development of degenerative lesions or the loss of insu- lin immunoreactivity. GLUT2 loss may be important in the deterioration of glucose-induced insulin secretion in the diabetic Chinese hamster. Key words Diabetic Chinese hamster - Pancreatic beta cell • Immunocytochemistry - Insulin - GLUT2 glucose transporter A. J6rns (~) Department of Anatomy I, Hannover Medical School, D-30623 Hannover, Germany M. Tiedge • S. Lenzen Institute of Clinical Biochemistry, Hannover Medical School, D-30623 Hannover, Germany E. Sickel Central Institute for Laboratory Animal Breeding, Hannover, Germany Introduction The Chinese hamster is an excellent animal model for NIDDM [8]. In previous morphological studies the changes in the pancreatic islets and the destruction of the beta cells during the development of diabetes have been documented [7, 9, 18, 19]. The degenerative beta cell lesions are accompanied by a deterioration of glucose-in- duced insulin secretion [6]. Together with glucokinase, the low-affinity plasma membrane GLUT2 glucose transporter in the pancreatic beta cell is responsible for recognition of glucose as the signal for glucose-induced insulin secretion [16, 17, 20]. Rat pancreatic beta cells display a dense immunostaining for GLUT2 in the cell membrane [12, 29] with a prefer- ential localization on microvillous domains [23]. In pan- creatic beta cells from various rat and mouse models of type I and type II diabetes a reduction or even a complete loss of GLUT2 expression has been described [13, 21, 22, 24, 25, 27, 30, 31]. No immunocytochemical studies on GLUT2 expression in beta cells in Chinese hamsters have been performed. In the present study, GLUT2 glucose transporter ex- pression has been studied by the use of immunocyto- chemical methods in semithin sections of pancreatic beta cells from normal and diabetic Chinese hamsters and in Western blots. We show that the development of diabetes in Chinese hamsters is accompanied by a concomitant reduction of GLUT2 immunoreactivity, which precedes the loss of insulin immunoreactivity and ultrastructural- ly, the development of the degenerative lesions in the af- fected beta cells. Materials and methods Animals Chinese hamsters aged 5-7 months and of both sexes (25-37 g body weight), bred in the Central Institute for Laboratory Animal Breeding in Hannover/Germany, were used. Animals were kept under standard laboratory conditions and had free access to food