Differential expression of rat pancreatic islet Beta-cell glucose transporter (GLUT 2), proinsulin and islet amyloid polypeptide genes after prolonged fasting, insulin-induced hypoglycaemia and dexamethasone treatment

Abstract

The question posed by these studies was whether chronic adaptive changes in glucose-stimulated insulin secretion are accompanied by comparable changes in islet Betacell glucose transporter (GLUT 2) gene expression. Control, fasted (3-day), insulin-injected hypoglycaemic (5-day), and dexamethasone-treated (4-day) rats (n=5 for each condition), were studied. After fasting significant decrements in proinsulin mRNA/μg RNA (-32 %, p<0.05) and islet amyloid polypeptide mRNA/μg RNA (-44%, p<0.05) were observed, while there was no change in GLUT 2 mRNA/μg RNA (-13%, p>0.05). After insulin-induced hypoglycaemia, decrements in proinsulin mRNA/μg RNA (-49%, p<0.01) and islet amyloid polypeptide mRNA/μg RNA (-44 %, p<0.01) were also observed, with no change in islet GLUT 2 mRNA/μg RNA (-18 %, p>0.05). Dexamethasone treatment resulted in a marked stimulatory effect on proinsulin mRNA/μg RNA (+236%, p<0.001) and islet amyloid polypeptide mRNA/μg RNA (+221 %, p<0.01), while again there was no change in islet GLUT 2 mRNA/μg RNA (+0.3%, p>0.05). Quantitative immunoblot analysis with a GLUT 2 specific antibody revealed no change in islet GLUT 2 protein with fasting, but a small decrease (-39±11%) in islet GLUT2/μg protein after insulin-induced hypoglycaemia. These results do not support the hypothesis that chronic changes in glucose-stimulated insulin secretion are accompanied by changes in GLUT 2 expression. In contrast to the lack of correlation with GLUT 2, there was a striking correlation between proinsulin and islet amyloid polypeptide mRNAs for all experimental conditions (r=0.974, p<0.001). These results suggest common transcriptional or turnover regulatory mechanisms or both for proinsulin and islet amyloid polypeptide gene expression, which differ for GLUT 2 gene expression. © 1992 Springer-Verlag.