ine . ▁Re asons ▁that ▁have ▁been ▁post ulated ▁in ▁the ▁literature ▁include ▁accum ulation ▁of ▁nit ric ▁ox ide ▁synth ase ▁in hib itor ▁due ▁to ▁high ▁gl uc ose ▁associated ▁kid ney ▁d ys function ▁and ▁reduced ▁production ▁of ▁nit ric ▁ox ide ▁synth ase ▁due ▁to ▁k eto ac idos is ▁observed ▁in ▁di ab etic ▁patients ▁and ▁p H ▁dependent ▁nature ▁of ▁nit ric ▁ox ide ▁synth ase . ▁ ▁Struct ural ▁and ▁functional ▁changes ▁in ▁fib ro bl asts ▁Di ab etic ▁ul cer ▁fib ro bl asts ▁show ▁various ▁morph ological ▁differences ▁compared ▁to ▁fib ro bl asts ▁from ▁age ▁matched ▁controls . ▁Di ab etic ▁ul cer ▁fib ro bl asts ▁are ▁usually ▁large ▁and ▁widely ▁spread ▁in ▁the ▁culture ▁flask ▁compared ▁to ▁the ▁sp ind le ▁sh aped ▁morph ology ▁of ▁the ▁fib ro bl asts ▁in ▁age - match ed ▁controls . ▁They ▁often ▁show ▁dil ated ▁end op las mic ▁ret icul um , ▁numerous ▁ves icular ▁bodies ▁and ▁lack ▁of ▁micro t ub ular ▁structure ▁in ▁transmission ▁electron ▁micro sc opy ▁study . ▁Therefore , ▁interpretation ▁of ▁these ▁observations ▁would ▁be ▁that ▁in ▁spite ▁of ▁high ▁protein ▁production ▁and ▁protein ▁turn over ▁in ▁di ab etic ▁ul cer ▁fib ro bl asts , ▁ves icles ▁containing ▁secret ory ▁prote ins ▁could ▁not ▁travel ▁along ▁the ▁micro t ub ules ▁to ▁release ▁the ▁products ▁outside . ▁F ib ro bl asts ▁from ▁di ab etic ▁ul cer ▁exhib it ▁pro l ifer ative