title: Left ventricular diastolic dysfunction in type 2 diabetes mellitus model rats.
abstract: To gain insight into the pathogenesis of diabetic cardiomyopathy, we investigated cardiac function in terms of the coupling of left ventricular mechanical work and the energetics in Otsuka Long-Evans Tokushima Fatty rats, which are well known as a model of type 2 diabetes mellitus (DM). Neither left ventricular systolic function and mean coronary flow nor coronary flow reserve differed even in late DM rats. The amount of oxygen required for mechanical work and contraction was unaltered, although myosin isozyme was finally transformed from V(1) to V(3). The maximum pacing rate was decreased from 300 to 240 beats/min, and the left ventricular relaxation rate was significantly (P < 0.05) slower only in late DM rats, resulting in decreased oxygen consumption per minute for total Ca(2+) handling in excitation-contraction coupling mainly consumed by sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA2) without significant changes in basal metabolism or in mitochondrial oxidative phosphorylation. The protein level of SERCA2 in membranes was significantly (P < 0.001) lower in severe DM rats. We conclude that the only lusitropic dysfunction due to the depressed expression of SERCA2 is related to generating diabetic cardiomyopathy even in the present type 2 diabetic rats.
authors.affiliation: Department of Physiology II, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan.
authors.forename: Takehisa
authors.initials: T
authors.lastname: Abe
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Ohga
authors.forename: Nobuoki
authors.initials: N
authors.lastname: Tabayashi
authors.forename: Shuichi
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Susumu
authors.initials: S
authors.lastname: Sakata
authors.forename: Hiromi
authors.initials: H
authors.lastname: Misawa
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Tsuji
authors.forename: Hisaharu
authors.initials: H
authors.lastname: Kohzuki
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Suga
authors.forename: Shigeki
authors.initials: S
authors.lastname: Taniguchi
authors.forename: Miyako
authors.initials: M
authors.lastname: Takaki
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002118:Calcium / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000276:immunology*; D004195:Disease Models, Animal; D004280:Dobutamine / Q000494:pharmacology; D006321:Heart / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D006439:Hemodynamics / Q000502:physiology*; D008297:Male; D009206:Myocardium / Q000201:enzymology; D009218:Myosins / Q000378:metabolism; D010101:Oxygen Consumption; D051381:Rats; D020334:Rats, Inbred OLETF; D020318:Rats, Long-Evans; D012016:Reference Values; D014655:Vascular Resistance; D018487:Ventricular Dysfunction, Left / Q000503:physiopathology*; D016277:Ventricular Function, Left / Q000502:physiology*
chemical_list: D004280:Dobutamine; D009218:Myosins; D002118:Calcium