Podocyte injury is putatively the main culprit in many progressive glomerulopathies (21) including DN. Using conventional methods, perhaps, the first recognizable podocyte alteration in DN is foot process effacement.
It is known that foot process effacement is accompanied by excess filtration of protein in ultrafiltrate. However, this may not be detectable in the terminal urine until the capacity of tubular protein reabsorption is surpassed. Foot processes are interconnected by slit diaphragm complexes, creating a zipper-like structure, which is thought to act as a sieve restricting the loss of large molecules into the urinary space. Nephrinuria can be detected in 30% of normoalbuminuric type 1 diabetic patients, suggesting early damage to the slit diaphragm (22). Foot process effacement is equivalent to reduced length density of slit diaphragms per GBM surface [Lv(SD/GBM)]. Consequently, reduced density of profiles of slit diaphragms would be seen on two-dimensional images of transmission electron microscope along the cross-section of GBM whenever foot process width is increased. This observation by many investigators has been expressed as reduced number of slits per GBM length, ignoring the fact that GBM is a complex three-dimensional structure, which is better characterized as a surface than a length. More disconcerting, a reduction in slit diaphragm length has been interpreted as reduced expression of components within the slit diaphragm rather than a decrease in the availability of the structure where these components reside. This critique is particularly applicable to reduced immunostainings for these molecules unless their quantitation is expressed in relationship to the available slit diaphragm structure.
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Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...