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Influence of IGF-1 supplementation on cardiac excitation-contraction coupling in diabetes. (Collegiate Communications--Undergraduate).

INTRODUCTION

Diabetes is one of the major risk factors leading to cardiovascular mortality and morbidity due to heart failure and vascular dysfunction (1). Diabetic cardiomyopathy is a myopathic state independent of macrovascular coronary artery complications and is the leading cause of death in both type I and type II diabetes (2). This disorder is characterized by decreased compliance, prolonged myocardial relaxation and altered intracellular [Ca.sup.2+] homeostasis and diastolic dysfunction is the most prominent mechanical defect (3). Insulin-like growth factor I (IGF-1) is known to promote growth and contraction in the cardiovascular system. However, the level of IGF-1 is attenuated in diabetes (4). The aim of the present study was to evaluate the cardiac contractile response of myocytes from diabetic and chronic IGF-1-supplemented diabetic cardiomyocytes.

METHODS

Male Sprague-Dawley rats were separated into four groups: control, control+IGF-1, diabetic and diabetic+IGF-1. A single injection of streptozotocin (STZ; 55mg/kg) was used to induce diabetes. Chronic IGF-1 supplementation (6mg/kg; every second day) was performed for six weeks. Single ventricular myocytes were isolated enzymatically from the hearts of all groups. Myocytes were electrically stimulated at 0.5 Hz and mechanical properties were evaluated using a video-based edge-detection system. Contractile properties analyzed included peak shortening (PS), time-to-90% PS (TPS), time-to-90% relengthening ([TR.sub.90]) and maximal velocities of shortening and relengthening ([+ or -] dL/dt). Intracellular [Ca.sup.2+] transients were measured as changes in fura-2 fluorescence intensity (?FFI).

RESULTS

The single injection of STZ caused massive weight loss and significantly increased blood glucose levels in animals in both diabetic groups. Diabetic animals showed significantly reduced PS and enhanced TPS and -dL/dt compared to control. Chronic supplementation with IGF-1 attenuated the PS and -dL/dt response. The fluorescence decay rate was significantly increased in diabetes, however IGF-1 also attenuated this response.

DISCUSSION

The blood glucose test confirmed the validity of this diabetic model. This is also supported by the mechanical dysfunction of ventricular myocytes from the diabetic animals, consistent with our previous reports using the same STZ model. IGF-1 ameliorated many of the devastating cardiac myopathic effects of diabetes, including altered cardiac contractility and intracellular [Ca.sup.2+] clearing. These results lend support to the cardioprotective effects of IGF-1 and its therapeutic potential in diabetic cardiomyopathy.

(1.) Alderman MH, et al. (1999) Hypertension, 33:1130-1134.

(2.) Fein FS, et al. (1981) Circ Res., 49:1251-1261.

(3.) Fein FS, et al. (1980) Circ. Res., 47:922-933.

(4.) Ren J (2000) Cardiovasc. Res., 46:162-171.

Sponsored by a fellowship to FN from the North Dakota Experimental Program to Stimulate Competitive Research and the American Diabetes Association.

Faye L. Norby *, Loren E. Wold, and Jun Ren Department of Pharmacology, Physiology, and Therapeutics University of North Dakota School of Medicine, Grand Forks
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Article Details
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Author:Norby, Faye L.; Wold, Loren E.; Ren, Jun
Publication:Proceedings of the North Dakota Academy of Science
Article Type:Brief Article
Geographic Code:1U4ND
Date:Apr 1, 2001
Words:457
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