THE DEVELOPMENT OF INSULIN-RESISTANCE WITH HIGH-FAT FEEDING IN RATS DOES NOT INVOLVE EITHER DECREASED INSULIN-RECEPTOR TYROSINE KINASE-ACTIVITY OR MEMBRANE GLYCOPROTEIN PC-1
B. Ozel et al., THE DEVELOPMENT OF INSULIN-RESISTANCE WITH HIGH-FAT FEEDING IN RATS DOES NOT INVOLVE EITHER DECREASED INSULIN-RECEPTOR TYROSINE KINASE-ACTIVITY OR MEMBRANE GLYCOPROTEIN PC-1, Biochemical and molecular medicine, 59(2), 1996, pp. 174-181
Recent studies have suggested that the insulin receptor tyrosine kinas
e inhibitor, membrane glycoprotein PC-1, may play a role in certain in
sulin resistant states. In the present study, we examined whether eith
er insulin receptor function or PC-1 activity was altered during the d
evelopment of insulin resistance that occurs with high fat feeding in
normal rats. Over the course of 14 days of high fat feeding, both maxi
mal and submaximal (physiological) insulin-stimulated skeletal muscle
glucose uptake decreased gradually; after 14 days of high fat feeding,
submaximal and maximal insulin-stimulated glucose uptake decreased by
similar to 40 and similar to 50%, respectively. In contrast, in the s
ame muscles (tibialis anterior) of these animals, neither insulin rece
ptor content nor insulin-stimulated insulin receptor autophosphorylati
on was altered after 14 days of high fat feeding. PC-1 has both nucleo
tide pyrophosphatase (EC 3.6.1.9) and alkaline phosphodiesterase I (EC
3.1.4.1) enzyme activities. These enzyme activities showed no changes
during the course of 14 days of high fat feeding. Individual data rev
ealed that there was no significant correlation between insulin-stimul
ated glucose uptake and alkaline phosphodiesterase or nucleotide pyrop
hosphatase activity (P > 0.05). Together, these data indicate that nei
ther defects in insulin receptor function nor elevated PC-1 activities
are involved in the development of insulin resistance in rats with hi
gh fat feeding, and the insulin resistance induced with high fat feedi
ng is likely due to postreceptor defects in Skeletal muscle. (C) 1996
Academic Press, Inc.