Intramuscular injection of soluble receptor for advanced glycation endproducts expression vector prevents the development of streptozotocin‐induced diabetes mellitus in rats on high fat diet

Background:  In order to study if advanced glycation endproducts (AGE) in high‐temperature cooked high fat diet could be the cause of type 2 diabetes, a expressing vector encoding soluble form of receptor for AGE (sRAGE) was injected intramuscularly, and the incidence of streptozotocin (STZ)‐induced diabetes mellitus in rats on high fat diet were observed. Methods:  Rat sRAGE gene, cloned to a pLNCX 2 expression vector (pLNCX 2 ‐sRAGE), was injected into the hind leg muscles of Sprague–Dawley rats. Rats were fed with high fat diet for 8 weeks before pLNCX 2 ‐sRAGE injection (designed as T group), or pLNCX2 (as H group), and rats on normal chow (as N group). The diet remained the same until end of the study. Serum malondialdehyde (MDA) and superoxide dismutase (SOD) levels were studied in one serial of rats ( n =  8) under the treatment of different vectors without STZ injection. For a second serial of study ( n =  20), rats were injected with 30 mg/kg STZ intraperitoneally 2 weeks after the second injection of vectors, and tail blood glucose was detected 1 week later. Results:  Malondialdehyde levels were found to be decreased 1 week after injection of sRAGE and lasted for at least 3 weeks after each injection. SOD activities were found to be increased slowly in the second week after each injection. As determined with fasting and random glycemia only two rats were in diabetic level (fasting glycemia ≥7.0 mmol/L and random glycemia ≥11.1 mmol/L) in T group while eight mice were in the diabetic level in H group. Conclusions:  Intramuscular injection of sRAGE decreases the MDA level and increases SOD activities, and decreases the STZ‐induced incidence of diabetes in rats in high fat diet.