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.
The question posed by these studies was whether chronic adaptive changes in glucose-stimulated insulin secretion are accompanied by comparable changes in islet Beta-cell 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/microgram RNA (-32%, p < 0.05) and islet amyloid polypeptide mRNA/microgram RNA (-44%, p < 0.05) were observed, while there was no change in GLUT 2 mRNA/microgram RNA (-13%, p > 0.05). After insulin-induced hypoglycaemia, decrements in proinsulin mRNA/microgram RNA (-49%, p < 0.01) and islet amyloid polypeptide mRNA/microgram RNA (-44%, p < 0.01) were also observed, with no change in islet GLUT 2 mRNA/microgram RNA (-18%, p > 0.05). Dexamethasone treatment resulted in a marked stimulatory effect on proinsulin mRNA/microgram RNA (+236%, p < 0.001) and islet amyloid polypeptide mRNA/microgram RNA (+221%, p < 0.01), while again there was no change in islet GLUT 2 mRNA/microgram 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 GLUT 2/microgram 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).(ABSTRACT TRUNCATED AT 250 WORDS)
D000682:Amyloid / Q000096:biosynthesis* / Q000235:genetics*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D015152:Blotting, Northern; D001835:Body Weight; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D005215:Fasting / Q000502:physiology*; D015870:Gene Expression / Q000187:drug effects; D007003:Hypoglycemia / Q000139:chemically induced / Q000503:physiopathology*; D007328:Insulin / Q000097:blood / Q000494:pharmacology*; D058228:Islet Amyloid Polypeptide; D007515:Islets of Langerhans / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D008099:Liver / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000096:biosynthesis* / Q000235:genetics*; D011061:Poly A / Q000235:genetics / Q000302:isolation & purification; D011384:Proinsulin / Q000096:biosynthesis* / Q000235:genetics*; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000682:Amyloid; D001786:Blood Glucose; D007328:Insulin; D058228:Islet Amyloid Polypeptide; D009004:Monosaccharide Transport Proteins; D012333:RNA, Messenger; D011061:Poly A; D012313:RNA; D003907:Dexamethasone; D011384:Proinsulin