Preservation of GLUT 2 expression in islet beta cells of Kilham Rat Virus (KRV) ? infected diabetes-resistant BB/Wor rats

Abstract

Summary Loss of GLUT 2, the glucose transporter isoform of pancreatic beta cells, has been reported to accompany the onset and perhaps contribute to the pathogenesis, of insulin-dependent and non-insulindependent diabetes mellitus in BB/Wor and Zucker fatty rats. In this study we investigated the effect of Kilham Rat Virus infection on GLUT 2 expression in diabetes-resistant BB/Wor rats. Viral antibodyfree diabetes-resistant rats do not develop spontaneous diabetes, but inoculation with Kilham Rat Virus induces autoimmune beta-cell destruction and hyperglycaemia. Pancreas sections from normoglycaemic diabetes-resistant BB/Wor rats were obtained 5, 7 and 25 days after inoculation with Kilham Rat Virus and stained for GLUT 2 using a rabbit polyclonal antibody. At all time points, beta cells displayed GLUT 2 expression comparable to uninfected diabetes-resistant controls. Immunostained insulin content of the beta cells also remained unchanged. Sections were also examined from Kilham Rat Virus inoculated diabetes-resistant rats with lymphocytic insulitis or diabetes. GLUT 2 and insulin immunostaining were unchanged in non-diabetic rats with early insulitis. GLUT 2 beta-cell staining was variably reduced in diabetic rats with established insulitis and reduced beta-cell insulin immunostaining. Hence, the initial stages of Kilham Rat Virus-induced diabetes in diabetes-resistant rats are not accompanied by a significant reduction in GLUT 2 expression. These results suggest that the loss of GLUT 2 does not play a significant role in the aetiology of diabetes in the Kilham Rat Virus-infected diabetes-resistant BB/Wor rat. [Diabetologia (1994) animal models of insulin dependent diabetes mellitus (IDDM) and non-insulin dependent diabetes mellitus (NIDDM) [4][5][6][7]. The Zucker diabetic fatty (ZDF) rat displays obesity and insulin resistance. Only male rats develop diabetes with an associated loss of insulin response to glucose [4]. Obese male diabetic ZDF rats revealed decreased beta-cell GLUT 2 protein and mRNA at the onset of diabetes, compared to obese non-diabetic female and lean non-diabetic male Zucker rats [4,6]. Glucose-induced insulin release in obese diabetic ZDF rats was correlated with the level of beta-cell GLUT 2; glucose-induced insulin release by the isolated perfused pancreas was absent in rats with fewer than 60 % GLUT 2 positive beta cells. In contrast, arginine infusions elicited a strong insulin secretory response,

Glucose transporters in pancreatic islets

“…In contrast to these studies, diabetes-resistant BB/Wor rats, treated with Kilham Rat virus to induce T1D did not show any alteration in the amount of GLUT2 + β-cells in the initial stage after virus infection [140]. A decrease in GLUT2 + β-cell mass became obvious with the onset of insulitis, arguing that GLUT2 is not essentially involved in the etiology of Kilham Rat virus-induced T1D [140].…”