The objective of the research project is to study the alteration of contractile and metabolic function of the cardiac and smooth muscles in rats with type I diabetes mellitus. Computational and experimental approaches are combined to investigate the relationship between disease and physiological and metabolic dysfunction of the muscles. Muscle electrical stimulation protocols are used to determine the active and passive biomechanical properties of the cardiac and smooth muscle. The parameters of the force-length and force–velocity relationships are determined while the mathematical model of Hodgkin–Huxley is used to quantify the relationship between tension, mechanical energy and velocity of the contractile apparatus in diabetic and control rats. The morphological and bioenergetic characteristics of heart mitochondrial are characterized in diabetic and control rats. Mitochondrial ultrastructural properties are determined with electron microscopy techniques while mitochondrial energetic function is determined using a polarographic system. These observations allow studying the relationship between mitochondrial morphology and function in diabetic rats. The mitochondrial experiments are fundamental to provide the data for computational modeling and analysis. The experimental data are integrated to a computational model of cardiac mitochondrial bioenergetics to study the regulatory mechanisms of the electron transport chain under physiological and pathophysiological conditions.
