Comparative effects of bile diversion and duodenal-jejunal bypass on glucose and lipid metabolism in diabetic rats (#21)
Aims: Duodenal-jejunal bypass (DJB) can induce rapid and durable improvement in glucose and lipid metabolism. Apart from bypassing the proximal gut, DJB also involves bile diversion (BD), which diverts bile acids (BAs) directly into the distal gut, resulting in increased intraluminal and systemic BAs that are essential to metabolic homeostasis. We have compared the metabolic outcomes of DJB and BD in a diabetic rat model, induced by high fat diet (HFD) and low dose streptozotocin (STZ).
Methods: HFD/STZ-induced diabetic rats were randomized to undergo DJB, BD (which diverted bile flow with an artificial tube to the same gut region of DJB) or SHAM procedures (n=10 each). Body weight and energy intake were monitored for 8 weeks. An intragastric glucose tolerance test (IGGTT) and an intragastric liquid meal test (IGLMT) were conducted before surgery, and at weeks 2 and 8. Blood glucose, serum insulin, GLP-1, lipid and BA concentrations were measured. Intraluminal BA content was evaluated at week 8.
Results: Intraluminal (distal gut) and serum BA concentrations were increased with both DJB and BD, and were higher after BD than DJB (P<0.05). Compared with SHAM, BD reducedbody weight by 5.3% (P<0.05), independently of energy intake, whereas DJB had no effect. During IGGTT, both fasting blood glucose and postprandial glucose concentrations were reduced after DJB and BD (P<0.05), and were lower after DJB than BD (P<0.05). HOMA-IR was reduced by 39±3.9% with DJB, but remained unchanged with BD or SHAM. Serum insulin concentrations were unaffected. During IGLMT, both fasting and postprandial (AUC) GLP-1 concentrations were increased after DJB and BD (P<0.05), without significant difference between BD and DJB. Hepatic and serum triglyceride, and serum free fatty acids were all decreased after DJB and BD versus SHAM, with hepatic triglyceride being lower, but serum triglyceride and free fatty acids higher, after DJB than BD (P<0.05).
Conclusions: BD, which increases intraluminal and systemic BA levels and enhances postprandial GLP-1 secretion, represents an important component of DJB in restoring glucose and lipid homeostasis. However, other mechanisms associated with DJB (eg. bypassing the proximal gut) also appear to make complementary contributions.