OBJECTIVE: To evaluate the effect of hepatic insulin gene therapy on diabetic enteric neuropathy. METHODS: Mice were randomly allocated into 3 groups: a normal control group, a diabetic group, and a diabetic gene therapy group. Diabetes were induced by penial vein injection of streptozocin (STZ). The gene therapy group received hepatic insulin gene therapy while the other 2 groups only received an empty virus expressing green fluorescent protein. Random blood glucose, body weight growth, gastric emptying, total bowel length, absolute and relative bowel transit, electric field stimulation of colon smooth muscle, colon nuclei staining and counting were measured. RESULTS: We successully established a mouse model of diabetic enteric neuropathy which manifests as: 8 weeks of continuous hyperglycemia,increased total bowel length, decreased relative bowel transit, impaired colon smooth muscle relaxation and loss of inhibitory neurons in colon. Through gene therapy, the above indexes were normalized or ameliorated, suggesting hepatic insulin gene therapy is capable of preventing diabetic enteric neuropathy. CONCLUSION Hepatic insulin gene therapy can prevent STZ induced diabetic enteric neuropathy.
Adenoviridae ; Animals ; Diabetes Mellitus, Experimental ; complications ; therapy ; Diabetic Neuropathies ; therapy ; Enteric Nervous System ; metabolism ; pathology ; Gastrointestinal Diseases ; etiology ; therapy ; Gene Transfer Techniques ; Genetic Therapy ; Genetic Vectors ; Hepatocytes ; metabolism ; Insulin ; genetics ; metabolism ; Mice ; Proinsulin ; genetics