Garcia_2012_Am.J.Physiol.Endocrinol.Metab_303_E551

Diabetic neuropathy is associated with functional and morphological changes of the neuromuscular junction NMJ associated with muscle weakness This study examines the effect of type 1 diabetes on NMJ function Swiss Webster mice were made diabetic with three interdaily ip injections of streptozotocin STZ Mice were severely hyperglycemic within 7 days after the STZ treatment began Whereas performance of mice on a rotating rod remained normal the twitch tension response of the isolated extensor digitorum longus to nerve stimulation was reduced significantly at 4 wk after the onset of STZ-induced hyperglycemia This mechanical alteration was associated with increased amplitude and prolonged duration of miniature end-plate currents mEPCs Prolongation of mEPCs was not due to expression of the embryonic acetylcholine receptor but to reduced muscle expression of acetylcholine esterase AChE Greater sensitivity of mEPC decay time to the selective butyrylcholinesterase BChE inhibitor PEC suggests that muscle attempts to compensate for reduced AChE levels by increasing expression of BChE These alterations of AChE are attributed to STZ-induced hyperglycemia since similar mEPC prolongation and reduced AChE expression were found for db/db mice The reduction of muscle end-plate AChE activity early during the onset of STZ-induced hyperglycemia may contribute to endplate pathology and subsequent muscle weakness during diabetes.