Myocardial hypertrophy and enhanced left ventricular contractility in Zucker diabetic fatty rats.
Heart failure is known to be a complication of insulin-dependent (IDDM) and noninsulin-dependent diabetes mellitus (NIDDM) even in the absence of coronary heart disease or hypertension. The mechanisms leading to diabetic cardiomyopathy are unknown. The aim of the study was to characterize structural and functional alterations in hyperinsulinemic Zucker diabetic fatty (ZDF) rats treated with or without insulin. Diabetic animals showed a twofold increase in cardiomyocyte volume with increased left ventricular ANP but not BNP mRNA levels in spite of a reduced plasma renin activity (PRA) 2 months after onset of diabetes compared to nondiabetic littermates. These changes were associated with an increase in left ventricular performance as assessed by echocardiography. Insulin treatment led to a significant increase in body weight (BW), total heart weight, myocardial protein content, and left ventricular mass (LVM). Perivascular fibrosis and laminin thickness were significantly augmented in diabetic rat myocardium irrespective of insulin treatment, whereas interstitial collagen I and fibronectin were similarly found in diabetic and control myocardium. Initial stages of diabetic cardiomyopathy in hyperinsulinemic rats are characterized by cardiomyocyte hypertrophy and enhanced cardiac contractility. It is suggested that hyperinsulinemia may be involved in cardiac hypertrophy.
Fredersdorf
Sabine
S
Klinik und Poliklinik für Innere Medizin II, Universitätsklinikum Regensburg, Franz-Josef-Strauss-Allee 11, D-93042, Regensburg, Germany.
Thumann
Christian
C
Ulucan
Coskun
C
Griese
Daniel P
DP
Luchner
Andreas
A
Riegger
Günter A J
GA
Kromer
Eckhard P
EP
Weil
Joachim
J
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism; D015152:Blotting, Northern; D006332:Cardiomegaly / Q000188:drug therapy / Q000209:etiology* / Q000473:pathology; D024042:Collagen Type I; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology; D004452:Echocardiography; D005353:Fibronectins; D005355:Fibrosis / Q000473:pathology; D006352:Heart Ventricles / Q000187:drug effects / Q000473:pathology; D006946:Hyperinsulinism / Q000503:physiopathology*; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D007328:Insulin / Q000627:therapeutic use; D007797:Laminin; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D009206:Myocardium / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011924:Rats, Zucker; D016276:Ventricular Function
D024042:Collagen Type I; D005353:Fibronectins; D007328:Insulin; D007797:Laminin; D012333:RNA, Messenger; D009320:Atrial Natriuretic Factor