Increased sensitivity of insulin-sensitive phosphodiesterase to insulin in fat cells from streptozotocin diabetic rats.
The effects of insulin on insulin-sensitive phosphodiesterase were investigated in fat cells from control and streptozotocin diabetic rats. Isolated cells were incubated at 37 C for 10 min, with and without insulin. A crude microsomal fraction prepared by differential centrifugation was assayed for phosphodiesterase activity. The enzyme activities in diabetic rats were higher at 0-1 nM insulin than in control rats. The dose-response curve of insulin was biphasic and of the convex type in both groups. In diabetic rats, the curve shifted to the left, and half-maximal stimulation was obtained at 0.06 nM insulin compared with 0.16 nM insulin in control rats. Kinetic analyses of the enzyme from diabetic rats revealed much the same findings as obtained in the controls. Specific binding of insulin in fat cells from control and diabetic rats was 3% and 4.9%/2 X 10(5) cells, respectively, at 24 C for 60-min incubation. Scatchard analysis indicates that the overall binding affinity in diabetic cells was greater than that in the control cells. These results suggest that the insulin effector system related to phosphodiesterase activation is intact and has an increased sensitivity in fat cells from streptozotocin diabetic rats; there is also a good correlation with alteration of insulin binding to its receptors.
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism*; D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology*; D007328:Insulin / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011972:Receptor, Insulin / Q000378:metabolism; D013552:Swine
D007328:Insulin; C008147:insulin, iodo-; D011972:Receptor, Insulin; D015105:3',5'-Cyclic-AMP Phosphodiesterases