Prostaglandylinositol cyclic phosphate synthase activity in the liver of insulin-resistant rhesus monkeys before and after a euglycemic hyperinsulinemic clamp.
Prostaglandylinositol cyclic phosphate (cPIP), functionally a cAMP antagonist, is a novel, low-molecular weight mediator of insulin action. Both essential hypertension and type 2 diabetes may be associated with a reduction of cPIP synthesis. In intact cells and in plasma membranes, cPIP synthesis is stimulated by insulin, which activates cPIP synthase by tyrosine phosphorylation. We measured the activities of cPIP synthase in the homogenates of freeze-clamped and then lyophilized liver samples from five insulin-resistant, adult rhesus monkeys, obtained under basal fasting conditions and again under maximal insulin stimulation during a euglycemic hyperinsulinemic clamp. The mean cPIP synthase activity in basal samples (0.33 +/- 0.09 pmol/min/mg protein) was not significantly different at the end of the clamp (0.24 +/- 0.11 pmol/min/mg protein). Basal cPIP synthase activityVoL 12, No. 1, 2001 was directly related to both basal cAMP content and basal fractional activity of cAMP-dependent protein kinase (PKA): r=0.85, p<0.05 and r=0.86, p<0.05, respectively. In turn, insulin-stimulated cPIP synthase activity was inversely related to both the insulin-stimulated fractional activity of PKA (r=0.89, p<0.02) and the insulin-stimulated total PKA activity: r=0.94, p<0.005. The findings suggest that in the liver of insulin-resistant rhesus monkeys, cPIP synthase activity, which leads to the synthesis of the low-molecular weight mediator cPIP, may oppose cAMP synthesis and PKA activity.
Shashkin
P N
PN
Obesity and Diabetes Research Center, Department of Physiology, University of Maryland School of Medicine, Baltimore 21201, USA. pshas001@umaryland.edu
Meckmongkol
T
T
Wasner
H K
HK
Hansen
B C
BC
Ortmeyer
H K
HK
D000818:Animals; D019729:Carbon-Oxygen Ligases / Q000378:metabolism*; D000242:Cyclic AMP / Q000096:biosynthesis; D017868:Cyclic AMP-Dependent Protein Kinases / Q000096:biosynthesis; D015309:Glucose Clamp Technique; D007333:Insulin Resistance / Q000502:physiology*; D008099:Liver / Q000201:enzymology*; D008253:Macaca mulatta; D008297:Male
D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D019729:Carbon-Oxygen Ligases; C110935:prostaglandylinositol cyclic phosphate synthetase