The Effects of Ileal Transposition on GLP-1 Analog Sensitivity and Cognitive Function in Diabetic Long Evans Rats

Obesity and Diabetes have become a major health problem which causes at least 230,000 deaths per year. According to the data from the American Diabetes Association (ADA), almost 8.3% of the population in America has type-2 diabetes. This number continues to increase every year. In 2007, the costs for diagnosed diabetes were 174 billion. It is estimated that the number of diabetic persons will reach 552 million in 2030. Among all the diabetic patients, 85-95% suffers from type 2 diabetes mellitus. Type 2 diabetes is a metabolic disorder in which the body no longer produces enough insulin (insulin deficiency) or fails to response to insulin (insulin resistance). It is also a major risk factor towards the development of Alzheimer\u27s disease which causes cognitive function impairment. The frontline treatment for obesity is commonly to change lifestyle and pharmacological agents. However, traditional treatments such as these are weak in their long term efficacy. In contrast, bariatric surgery has become an increasing popular option and provides sustained benefits, such as massive and durable body weight loss and control of blood glucose. Bariatric surgery elicits body weight loss through restricting the size of the stomach (Gastric Banding) or by bypassing the upper intestine (RYGB). Ileal transposition surgery (IT) avoids restriction and malabsorption by translocating a 10cm ileal segment to the position between duodenum and jejunum. The mechanism is based on the hindgut hypothesis. This surgery stimulates Glucagon-like Peptide-1 (GLP-1) secretion which enhances insulin secretion. GLP-1 is also a neuroprotective factor which can decrease the brain cognitive and learning impairment. Because endogenous GLP-1 is elevated, we hypothesis 1) diabetic rats receiving ileal transposition would exhibit reduced sensitivity to a GLP-1 analog (exendin-4) and 2) the rats with ileal transposition may display improved cognitive function compared to sham-operated rats. Though the experiments such as food intake and body weight measurements and oral glucose tolerance test in 4 and 13.5 month, we observed exendin-4 decreased food intake and body weight in diabetic rats and exendin-4 sensitivity was limited after IT surgery. Though the Morris Water Maze test and probe test, we observed the improved cognitive function long term after IT surgery in diabetic rats