**7. Cardiac muscle**

In order to appreciate how diabetes-induced hyperglycemia is inducing fibrosis and cardiomyopathy, it is paramount importance to understand first, the structure of the cardiac cell or cardiomyocyte. Cardiac muscle, at the microscopic level, can be described as a composite tissue. It is made of various cell types, mainly myocytes and fibroblasts which are supported by extracellular matrix (ECM), all of which are permeated by fluids [15]. The myocardial ECM is made of macro-molecules which are produced by local fibroblasts. They consist of a fibrillar collagen network, a basement membrane and proteoglycans [20]. The function of the fibrillar collagen network is to strengthen the matrix, thereby giving strong structural support of the adjoining cardiomyocytes and the means by which they shorten to exert their contractile effect efficiently during ventricular pump action and thus, contributes to myocardial diastolic stiffness [21]. The heart is composed of different types of collagens including fibrillar collagen type I with the tensile strength of steel and fibrillary collagen type III which is the most abundant phenotypes [21]. Secondly, the basement membrane which surrounds the myocyte is attached to the sarcolemma and to the fibrillar collagen network. The myocyte adherence to basement membrane is a major determinant in maintaining cell shape and positional integrity within the ventricular wall [22]. Thirdly, the proteoglycans are composed of a protein core to which polysaccharide chains called glycosaminoglycans are covalently bound. These negatively charged molecules possess significant osmotic activity helping to trap and to store growth factors within ECM. Proteoglycan molecules in the connective tissue form a highly hydrated, gel-like "ground substance" in which the fibrous proteins are embedded. [22, 23]. The function of the polysaccharide gel is to prevent any compressive forces on the matrix thereby allowing the rapid diffusion of nutrients, metabolites and hormones between the blood and the cardiac tissue cell [23].
