Defect in long-term activation of phosphatidylinositol 3-kinase by insulin in vivo: studies in insulin-resistant hHTg rats.
OBJECTIVE
To study the regulation of phosphatidylinositol (PI) 3-kinase by insulin in vivo in hereditary hypertriglyceridemic and insulin resistant rat (hHTg).


METHODS
Total and insulin receptor substrate-1 (IRS-1) associated PI 3-kinase activities were measured in skeletal muscles and adipose tissue after an intense insulin induced glucose utilization as accomplished by 90 min euglycemic hyperinsulinemic clamp.


RESULTS
In quadriceps femoris muscle, no stimulation of total or IRS-1 associated PI 3-kinase activities was found after hyperinsulinemia in both hHTg and control rats. In contrast, in soleus muscle of control rats total PI 3-kinase activity was stimulated by insulin (P<0.001), while any such effect was not found in hHTg rats. IRS-1 associated PI 3-kinase activity in soleus muscle was significantly decreased in hHTg rats when compared to control rats (P<0.001), but was not affected by insulin. In white adipose tissue (WAT), both the total (P<0.05) and IRS-1 associated PI 3-kinase activities (P<0.001) were increased after 90 min hyperinsulinemia in control animals but not in hHTg animals.


CONCLUSIONS
Long-term activation of PI 3-kinase activity by insulin in vivo involves IRS-1 in white adipose tissue, but not in skeletal muscle which implies tissue specificity. The impairment in the PI 3-kinase activation by insulin in hHTg rats may participate in insulin resistance of these animals.
Sebokova
E
E
Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava, Slovakia. ueensebo@savba.savba.sk
Gasperikova
D
D
Ouwens
M
M
Dorrestijn
J
J
Eckel
J
J
Maasen
A
A
Klimes
I
I
D000273:Adipose Tissue / Q000187:drug effects / Q000201:enzymology; D000818:Animals; D004195:Disease Models, Animal; D004789:Enzyme Activation; D015309:Glucose Clamp Technique; D015228:Hypertriglyceridemia / Q000235:genetics*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D055504:Insulin Receptor Substrate Proteins; D007333:Insulin Resistance / Q000235:genetics*; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000201:enzymology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011972:Receptor, Insulin / Q000378:metabolism; D013997:Time Factors
D007004:Hypoglycemic Agents; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; D010750:Phosphoproteins; D019869:Phosphatidylinositol 3-Kinases; D011972:Receptor, Insulin