Alterations in insulin receptor and substrate phosphorylation in hypertensive rats.
Insulin stimulates tyrosine phosphorylation of the insulin receptor and of an endogenous substrate of approximately 185 kd (insulin receptor substrate 1 or IRS-1) in most cell types. Tyrosine phosphorylation of insulin receptor and of IRS-1 have been implicated in insulin signal transmission based on studies with insulin receptor mutants. In the study presented here, the levels and phosphorylation state of the insulin receptor and IRS-1 in liver and muscle after insulin stimulation in vivo have been examined in spontaneously hypertensive rats (SHR) by immunoblotting with antipeptide antibodies to insulin receptor and IRS-1 and antiphosphotyrosine antibodies. It was found that the levels of insulin receptor and IRS-1 protein in liver and muscle are similar in controls (Wistar-Kyoto rats) and SHR. By contrast, there is a decrease in autophosphorylation in the liver and muscle of SHR and a parallel decrease in phosphorylation of IRS-1. These data indicate that reduced insulin receptor kinase activity and reduced substrate phosphorylation may play an important role in the impaired insulin action in the hypertensive rat.
Kahn
C R
CR
Research Division, Joslin Diabetes Center, Boston, MA 02215.
Saad
M J
MJ
D000818:Animals; D006973:Hypertension / Q000378:metabolism*; D007333:Insulin Resistance; D010766:Phosphorylation; D051381:Rats; D011918:Rats, Inbred SHR; D011972:Receptor, Insulin / Q000378:metabolism*; D013379:Substrate Specificity; D014443:Tyrosine / Q000378:metabolism
D014443:Tyrosine; D011972:Receptor, Insulin