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Insulin signaling in Goto‐Kakizaki rat model of type II diabetes
Author(s) -
Kelly Aisha Imani,
PortikDobos Vera,
Mezzetti Erin,
Ergul Adviye
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1226.42
Subject(s) - medicine , endocrinology , insulin resistance , protein kinase b , insulin , insulin receptor , phosphorylation , diabetes mellitus , skeletal muscle , glucose uptake , carbohydrate metabolism , irs1 , type 2 diabetes , glucose clamp technique , chemistry , insulin receptor substrate , pancreatic hormone , biochemistry
Aberrant insulin signaling is a hallmark of insulin resistance. Decreased phosphorylation of insulin receptor substrate (IRS‐1) proteins and Akt, in particular, results in reduced glucose uptake by the tissues thereby contributing to the insulin resistant state. We have previously shown that insulin‐mediated aortic relaxation is reduced in Goto‐Kakizaki (GK) rat model of Type II diabetes. This study tested the hypothesis that blunted insulin signaling contributes to impaired vascular function and glucose metabolism in this lean model of diabetes. In GK rats, blood glucose was higher (168 ± 5 vs. 108 ± 3 mg/dl, p<0.05) and hyperinsulinemic euglycemic clamp studies showed decreased glucose utilization indicative of insulin resistance. Assessment of total and phosphorylated (p) IRS‐1 and Akt expression in aorta, liver, and skeletal muscle showed that IRS‐1 activation (pIRS‐1/total IRS‐1) was significantly decreased in all tissues as compared to Wistar controls (n= 4–5, p<0.05). Similarly, Akt activation (pAkt/total Akt) was reduced in the aorta and the liver (p<0.05). Akt activation in skeletal muscle, however, was significantly increased in GKs (p<0.05), suggesting a possible compensatory mechanism to promote peripheral glucose utilization.