Type 2 diabetes caused by obesity shows autonomic neuropathy. Molecular mechanism involved in enteric neurodegeneration is not clear. Neuronal nitric oxide synthase (nNOS) is one of the important agents involved in gastrointestinal function. Therefore, expression of nNOS in the duodenum LM-MP of type 2 diabetes model mouse was studied. Real time RT-PCR analysis showed reduction in nNOS expression in male diabetic LM-MP compared to male control. In contrast, female diabetic LM-MP had high level of nNOS mRNA compared to female control. Western blot determination of LM-MP showed reduction in nNOS protein in male diabetic LM-MP and high level of nNOS in female diabetic LM-MP compared to their respective controls. Expression of nNOS observed by Western blot was further confirmed by nNOS immunostaining of the mouse duodenum. TUNEL staining of mouse duodenum showed apoptosis in male diabetic enteric neurons. These studies suggest that nNOS expression in LM-MP varies with gender during early stage of type 2 diabetes. In addition, reduced expression of nNOS is likely to contribute to apoptosis seen in the enteric neurons of male type 2 diabetic mice. (c) 2005 Elsevier Inc. All rights reserved.