Differential expression of rat insulin I and II messenger ribonucleic acid after prolonged exposure of islet beta-cells to elevated glucose levels.
Prolonged exposure of rat islet beta-cells to 10 mmol/liter glucose has been previously shown to activate more cells into a glucose-responsive state (>90%) than has exposure to 6 mmol/liter glucose (50%). The present study demonstrates that this recruitment of more activated cells results in 4- to 6-fold higher levels of proinsulin I and proinsulin II messenger RNA (mRNA). However, only the rate of proinsulin I synthesis is increased. Failure to increase the rate of proinsulin II synthesis in the glucose-activated cells results in cellular depletion of the insulin II isoform, which can be responsible for degranulation of beta-cells cultured at 10 mmol/liter glucose. Higher glucose levels (20 mmol/liter) during culture did not correct this dissociation between the stimulated insulin I formation and the nonstimulated insulin II formation. On the contrary, the rise from 10 to 20 mmol/liter glucose resulted in a 2-fold reduction in the levels of proinsulin II mRNA, but not of proinsulin I mRNA; this process further increased the ratio of insulin I over insulin II to 5-fold higher values than those in freshly isolated beta-cells. The present data suggest that an elevated insulin I over insulin II ratio in pancreatic tissue is a marker for a prolonged exposure to elevated glucose levels. The increased ratio in this condition results from a transcriptional and/or a posttranscriptional failure in elevating insulin II formation while insulin I production is stimulated in the glucose-activated beta-cells.
Ling
Z
Z
Diabetes Research Center, Vrije Universiteit Brussel, Brussels, Belgium.
Heimberg
H
H
Foriers
A
A
Schuit
F
F
Pipeleers
D
D
D000818:Animals; D002478:Cells, Cultured; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000235:genetics* / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism*; D007536:Isomerism; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D007328:Insulin; D012333:RNA, Messenger; D005947:Glucose