Effect of insulin treatment on systolic and diastolic function of left ventricular cardiomyocytes in diabetic rats

Abstract

Objective To explore the effect of insulin treatment at low doses on systolic and diastolic function of left ventricular cardiomyocytes,myocardial ultrastructure and the whole cardiac function in diabetes rats.Methods Twenty-five rats were randomly divided into three groups:diabetes mellitus(DM) group(n =9),insulin treatment(INS) group(n =9) and control(CN) group(n =7).The rats in INS group were hypodermically injected with insulin since the DM models were established through intraperitoneal injection of streptozotocin.Echocardiography,video-based edge-detector system and transmission electron microscope were performed respectively at the point of week 8 to observe the changes of myocardial ultrastructure,systolic and diastolic function of cardiomyocytes as well as changes of whole cardiac structure and function in left ventricle(LV).Results Echocardiography suggested that in contrast to CN group,DM group showed larger LV end-systolic diameter (LVESD)and end-diastolic diameters (LVEDD) [LVEDD:(6.00 ± 0.54)mm vs (4.89 ± 0.29)mm; LVESD:(3.90 ± 0.53)mm vs (2.39 ± 0.41) mm,respectively],thinner systolic interventricular septum(IVSs) [(2.11 ± 0.24)mm vs (3.04 ± 0.31)mm] and LV posterior wall(LVPWs) [(2.16 ± 0.20) mm vs (2.94 ± 0.28) mm],and decreased LV ejection fraction (LVEF)[(63.5 ± 8.4)％ vs (82.3 ± 6.1)％](all P ＜0.05).INS group indicated smaller LVESD[(3.21 ± 0.44)mm vs (3.90± 0.53)mm] and increased LVEF[(71.5 ± 8.5)％ vs (63.5 ± 8.4)％] compared to DM group(all P ＜0.05).Furthermore,single cardiomyocyte function assessments demonstrated that cell length [(113.88 ± 13.05)μm vs (128.72 ± 11.62)μm] shortened,peak shortening value(PS％) [(6.61 ± 1.45) ％ vs (8.65 ± 1.29)％] and maximal velocity of shortening and relengthening (± dL/dt) [+ dL/dt:(235.35 ± 81.76)μm/s vs (413.33 ± 71.33)μm/s;-dL/dt(-195.60 ± 72.81)μm/s vs (-316.53 ± 56.11)μm/s] reduced,and time to peak shortening (TPS) [(177.11 ± 30.36) ms vs (119.34 ± 25.27) ms] together with time from peak to 90％ relaxation(TR90)[(186.98 ± 39.17)ms vs (136.89 ± 35.61)ms] prolonged in the DM group compared with CN group (all P ＜0.05).While INS group ameliorated abnormalities of cell length [(119.86± 12.61) μm vs (113.88 ± 13.05)μm],PS％ [(7.26 ± 1.34)％ vs (6.61 ± 1.45)％],+ dL/dt [(294.25±68.11)μm/s vs (235.35 ± 81.76)μm/s],dL/dt[(240.34± 71.31)μm/s vs (-195.60± 72.81)μm/s],TPS[(160.10 ± 28.19)ms vs (177.11 ± 30.36)ms] and TR90 [(168.26 ± 38.05)ms vs (186.98 ± 39.17)ms] compared with DM group (all P ＜0.05).Moreover,transmission electron microscope indicated that DM group showed fractured and dissolved myofilament,swollen and aggregated mitochondria and deposited collagen fibers and glycogen granules.But myocardial ultrastructure abnormalities in INS group were ameliorated compared with DM group.Conclusions Low doses insulin treatment could ameliorate the abnormalities of structure and function in diabetic myocardium so that this could moderate diabetic myocardial damage and show a cardioprotective effective role of low doses insulin in diabetic mellitus. Key words: Echocardiography; Diabeties mellitus; Insulin; Ventricular function, left; Myocytes,cardiac