Mechanisms that may be involved in calcium tolerance of the diabetic heart.

摘要: In diabetes the hearts exhibit impaired membrane functions, but also increased tolerance to Ca2+ (iCaT) However, neither true meaning nor molecular mechanisms of these changes are fully understood. The present study is devoted elucidation alterations, particularly those induced by non-enzymatic glycation proteins, that may be responsible for iCaT rat in stage developed, still compensated diabetic cardiomyopathy (DH). Insulin-dependent (DIA) was a single i.v. dose streptozotocin (45 mg.kg-1). Beginning with subsequent day, animals obtained 6 U insulin daily. Glucose, triglycerides, cholesterol and glycohemoglobin were investigated blood. ATPase activities, kinetics activation (Na,K)-ATPase Na+ K+, further fluorescence anisotropy diphenyl-hexatriene as well order parameters membranes isolated heart sarcolemma (SL) investigated. addition, degree glycation-related potency radical generation SL proteins determined investigating their fructosamine content. calcium DH ‘transparent’ model, subjected paradox (Ca-Pa, 3 min depletion; 10 repletion). this model Ca2+-overload, ions enter cardiac cells way not mediated receptors. Results revealed more than 83% perfused recovered, while non-DIA control all failed after Ca-Pa. exhibited preserved activities Na+, even This considered reason iCaT. Pretreatment administration resorcylidene aminoguanidine (RAG 4 or 8 mg.kg-1) during disease prevented partially pathobiochemical effects DIA-induced proteins. perturbations completely RAG (4 Although, latter treatment exerted little influence on activity, it decreased DH. supporting our hypothesis glycation-induced enhancement free formation protein crosslinking participate adaptive ‘positive’ (Mol Cell Biochem 176: 191–198, 1997)