A Simple Proximal Intestinal Bypass Surgery Directly Improves Insulin Sensitivity and Insulin Secretion in Mice

Objectives: To verify foregut hypothesis, we conducted simple bariatric surgery to evaluate the effects of those operations on body weight, glucose tolerance and insulin sensitivity in mice. Methods: We applied operation techniques which involved gastrojejunostomy (GJ), GJ with duodenojejunal exclusion (GJDE), and sham operation (control). Jejunostomy site was located in the mid-jejunum with 1.0 cm pore size. Three different fed conditions were applied; 1) C57BL/6 mice fed with 60% high-fat diet (HFD) before and after surgery (n=8). ICR mice had been fed with chow diet, followed by 2) 45% HFD (n=9), and 3) 60% HFD (n=12) after surgery. Results: In HFD fed C57BL/6 mice, body weight following operations was significantly reduced during first 2 weeks in GJDE and GJ mice compared to control mice, thereafter the difference was gradually attenuated. OGTT and ITT at 5 and 7 weeks after surgery showed that glucose levels were significantly lower, and insulin sensitivity was significantly improved in GJ and GJDE mice compared to control. In addition, in response to high glucose administration, insulin level was significantly increased in GJ and GJDE mice. In lean ICR mice, body weight in GJ and GJDE operated mice (45% HFD after surgery) were significantly lowered than that of control mice since 3 weeks after surgery. There were no difference in glucose tolerance between groups until 7 weeks, however, AUC glucose were significantly lower in GJDE mice than GJ and control mice after 10 weeks. ITT also showed GJDE mice were more insulin sensitive than GJ and control mice. GJ and GJDE operated mice with 60% HFD after surgery also showed similar results indicating delayed improvement in insulin sensitivity with proximal intestinal bypass. Conclusion: This simple operation of proximal intestinal bypass demonstrated its effects on improvement in glucose tolerance and insulin sensitivity in mice. Mice preconditioned with HFD before surgery was also benefited by improvement in insulin secretion. Disclosure H. Jang: None. N. Ha: None. M. Song: None. H. Lee: None. B. Jin: None. D. Kim: None. N. Kim: None.