ODP228 Obesity Induced a Down-Regulation of nNOS in Intrapancreatic Nervous System

OBJECTIVE: Obesity has become a serious global public health problem. Obesity is frequently preceding and the most important risk factor of type 2 diabetes. Pancreas regulates glucose metabolism and glucose homeostasis, and abnormality of pancreas play an important role in insulin resistance and diabetes. Intrapancreatic nerve innervation modulates insulin release and is tightly linked to the onset and development of diabetes. However, it is not known whether the activity of the intrapancreatic nervous system has been altered before the onset of diabetes. In this study, we examined the intrapancreatic nervous system in rats with obesity looking for the changes induced by obesity. METHODS: Obese Sprague-Dawley rats were developed with feeding high fat diet for 10 weeks. Using Immunofluorescence method, choline acetyl transferase (ChAT) and nNOS positive neurons in intrapancreatic ganglia were counted. ChAT and nNOS expression in pancreas were also measured with western blot method. RESULTS: (1) There was no significant difference in fasting blood glucose between obese rats and normal rats, but oral glucose tolerance test showed that the oral glucose tolerance was impaired in obese rats. (2) In rats fed with normal diet, 80.2%±1.5 neurons in intrapancreatic ganglia were ChAT positive, and in the obese rats, 79.3%±1.8 neurons were ChAT positive. There was no significant difference between the two groups (p>0. 05, n=5). In intrapancreatic ganglia of obese rats, 40%±1.4 neurons were nNOS positive, which was significantly lower than that (60.5%±1.2) of rats fed with normal diet (p<0. 01,n=5). (3) In pancreatic tissue, the relative expression level of ChAT protein was 1. 02±0. 03 in rats fed with normal diet and 0.98±0. 05 in obese rats (p>0. 05, n=5). The relative expression level of nNOS protein was 1.70±0. 08 in normal rats and 1.10±0. 05 in obese rats (p>0. 01, n=5). CONCLUSION: The cholinergic nerves in intrapancreatic nervous system was not altered in obese rats, however, nNOS nerves was down-regulated in obese rats. The down-regulation of nNOS would induce a hyperactivity in intrapancreatic nervous system and this would cause an enhancement of insulin release, which has been observed in obese individuals. Presentation: No date and time listed