Diabetes, Vol 44, Issue 10 1196-1201, Copyright © 1995 by American Diabetes Association
Regulation of insulin receptor mRNA splicing in rat tissues. Effect of fasting, aging, and diabetes
H Vidal, D Auboeuf, M Beylot and JP Riou
INSERM, Faculte de Medecine Alexis Carrel, Lyon, France.
Recent findings suggested that alterations in insulin receptor isoform
expression might be involved in the molecular mechanism of insulin
resistance. Using reverse transcription reaction followed by competitive
polymerase chain reaction, we measured the level of the receptor mRNA
variants in rat insulin-sensitive tissues, under conditions of decreased
insulin effectiveness (fasting, aging, and diabetes). The liver expressed
the mRNA variant with exon 11 predominantly, and the hind limb skeletal
muscles expressed the mRNA without exon 11. The heart and epididymal
adipose tissue expressed both variants. Fasting and streptozocin-induced
diabetes increased the level of receptor mRNAs in the liver but did not
modify the repartition between the two variants. The modification of the
expression ratio, in favor of the form with exon 11, found by some authors
in the skeletal muscle of insulin-resistant patients was not observed in
rat muscles that expressed > 99% of the form without exon 11 under all
the conditions tested. In adipose tissue, the proportion of both mRNA
variants was never altered (45% of exon 11-positive [Ex11+]), while the
total receptor mRNA concentration changed markedly during fasting or aging.
The only modification observed in the isoform distribution was a
significant decrease in Ex11+ mRNA concentration in the liver, muscle, and
heart of old rats. We conclude that alternative splicing of insulin
receptor mRNA is not involved in the impairment of insulin action during
fasting or diabetes. Its potential role in the insulin resistance of old
animals remains to be defined.