Reduced contractile response to insulin and IGF-I in ventricular myocytes from genetically obese Zucker rats

• Published in: American journal of physiology. Heart and circulatory physiology Vol. 279; no. 4; pp. H1708 - H1714
• Main Authors: Ren, Jun, Sowers, James R, Walsh, Mary F, Brown, Ricardo A
• Format: Journal Article
• Language: English
• Published: United States 01.10.2000
• Subjects: Animals; Calcium - metabolism; Female; Fluorescence; Insulin - pharmacology; Insulin-Like Growth Factor I - pharmacology; Intracellular Membranes - metabolism; Myocardial Contraction - drug effects; Myocardium - metabolism; Myocardium - pathology; Obesity - genetics; Obesity - pathology; Obesity - physiopathology; Rats; Rats, Zucker; Receptor, IGF Type 1 - genetics; Reference Values; RNA, Messenger - metabolism; Ventricular Function - drug effects
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.2000.279.4.h1708

1  Department of Pharmacology, Physiology, and Therapeutics, University of North Dakota School of Medicine, Grand Forks, North Dakota 58203; 2  State University of New York Downstate Medical Center, Brooklyn, New York 11203-2098; and Departments of 3  Internal Medicine and 4  Physiology, Wayne State University School of Medicine, Detroit, Michigan 48201 Obesity plays a pivotal role in the pathophysiology of metabolic and cardiovascular diseases. Resistance to insulin is commonly seen in metabolic disorders such as obesity and diabetes. Insulin-like growth factor-I (IGF-I) mimics insulin in many tissues and has been shown to enhance cardiac contractile function and growth. Because IGF-I resistance often accompanies resistance to insulin, we sought to determine whether IGF-I-induced myocardial contractile was elevated and whether heart and kidney size were enlarged in obese compared with lean rats. The myocyte contraction profile in the obese rats showed a decreased peak shortening associated with prolonged relengthening and normal shortening duration, a pattern similar to that observed in diabetes. IGF-I (1-500 ng/ml) caused a dose-dependent increase in peak shortening in lean but not obese animals, but it did not alter the duration of shortening and relengthening. Consistent with contractile data, IGF-I induced a dose-dependent increase in Ca 2+ transients only in myocytes of lean rats. IGF-I receptor mRNA levels were significantly reduced in obese rat hearts. These results suggest that the IGF-I-induced cardiac contractile responses are attenuated in the Zucker model of obesity. The mechanisms underlying this alteration may be related to the decreased receptor number and/or changes in intracellular Ca 2+ handling in these animals. insulin-like growth factor-I; myocyte shortening; intracellular calcium transients; insulin-like growth factor-I receptor