Mechanisms of the defect in cardiac myofibrillar function during diabetes.
Diabetes was induced in rats by an intravenous injection of streptozotocin (65 mg/kg body wt), and animals were killed 8 wk later. Some animals were maintained in a diabetic state for 6 wk and then given 2 wk of insulin treatment in vivo. Myofibrils were isolated and ATPase activities measured. Mg2+-ATPase and Ca2+-stimulated ATPase activities were depressed in diabetic rat hearts in comparison to control; insulin treatment normalized these activities. The depression in myofibrillar ATPases was of gradual onset as no changes were detected 2 wk after inducing diabetes. Treatment of diabetic animals with thyroid hormone did not restore changes in myofibrillar ATPase activities. Marker enzyme activities did not reveal any detectable contamination by cardiac membranes. Mg2+-ATPase activity of myofibrillar preparations from control and diabetic hearts responded differently to N-ethylmaleimide modification. Furthermore, myofibrillar sulfhydryl reactivity to 5,5'-dithiobis(2-nitrobenzoic acid) was significantly depressed in diabetic preparations in comparison to control and insulin-treated diabetic animals. These results suggest that the defect in myofibrillar ATPase activities in chronic diabetes may be due to some modification of sulfhydryl groups.
Pierce
G N
GN
Dhalla
N S
NS
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D001696:Biomechanical Phenomena; D017301:Ca(2+) Mg(2+)-ATPase; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology / Q000378:metabolism / Q000503:physiopathology*; D004228:Dithionitrobenzoic Acid / Q000494:pharmacology; D005033:Ethylmaleimide / Q000494:pharmacology; D006321:Heart / Q000503:physiopathology*; D008297:Male; D009210:Myofibrils / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D013311:Streptozocin; D013438:Sulfhydryl Compounds / Q000378:metabolism
D013438:Sulfhydryl Compounds; D013311:Streptozocin; D004228:Dithionitrobenzoic Acid; D000251:Adenosine Triphosphatases; D017301:Ca(2+) Mg(2+)-ATPase; D000252:Calcium-Transporting ATPases; D005033:Ethylmaleimide