Signals derived from glucose metabolism are required for glucose regulation of pancreatic islet GLUT2 mRNA and protein.
Pancreatic islet GLUT2 mRNA is known to be regulated in vitro and in vivo by glucose. We have investigated several potential mechanisms mediating the response of islet GLUT2 to glucose. GLUT2 mRNA and protein were measured from isolated rat islets cultured for up to 24 h under selected conditions. Glucose at 11 mM stimulated GLUT2 mRNA 10-fold compared with 2 mM glucose, with no additional increase at 16.7 mM glucose, whereas maximal 4-fold induction of the protein was attained with 16 mM glucose. Time course studies showed a 2.5-fold induction of GLUT2 mRNA apparent after only 8 h of culture at 16.7 mM glucose. Glycolysis inhibitor mannoheptulose suppressed the stimulatory effect of 16.7 mM glucose on GLUT2 mRNA and protein. Metabolizable sugars mannose and glyceraldehyde enhanced transporter mRNA levels, in contrast with the lack of stimulation by nonmetabolizable 2-deoxy-D-glucose. Stimulation by different sugars and glycolysis inhibition led to analogous changes of proinsulin mRNA, suggesting that common signaling mechanisms are shared in glucose regulation of proinsulin and GLUT2 gene expression. Preexposure to mannoheptulose, however, failed to suppress glucose-stimulated insulin release. Tunicamycin, a glycoprotein synthesis inhibitor, did not block the effect of 16 mM glucose on GLUT2 mRNA levels. RNA and protein synthesis inhibitors actinomycin and cycloheximide abolished the enhancing effects of high glucose on GLUT2 mRNA. These findings indicate that glucose metabolism, but not glycoprotein synthesis or substrate interaction with the transporter protein, is instrumental in the stimulatory effects of glucose on beta-cell GLUT2 mRNA accumulation. In addition, ongoing RNA and protein synthesis are required for this effect.
Ferrer
J
J
Endocrinology and Nutrition Unit, University of Barcelona School of Medicine, Spain.
Gomis
R
R
Fernández Alvarez
J
J
Casamitjana
R
R
Vilardell
E
E
D000818:Animals; D005947:Glucose / Q000378:metabolism*; D051273:Glucose Transporter Type 2; D006019:Glycolysis / Q000187:drug effects; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000235:genetics*; D014176:Protein Biosynthesis; D011506:Proteins / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology*
D051273:Glucose Transporter Type 2; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D011506:Proteins; D012333:RNA, Messenger; D005947:Glucose