OBJECTIVETo evaluate the effect and possible mechanisms of diabetes control after small intestine exclusion surgery in Goto-Kakizaki (GK) rat with non-obese type 2 diabetes mellitus.

METHODSForty GK rats with non-obese type 2 diabetes mellitus underwent duodenal bypass (Group A, n = 8), which creates a shortcut for ingested nutrients bypassing duodenum alone; duodenal-jejunal bypass (Group B, n = 8), a stomach-preserving RYGB that excludes the duodenum and proximal jejunum; duodenum and total jejunum exclusion (Group C, n = 8); sub-total small intestine exclusion (Group D, n = 8), which creates a shortcut for ingested nutrients bypassing duodenum, jejunum and sub-total ileum; controls were pair-fed (PF) sham-operated and untreated GK rats (Group SO, n = 8). The rats were observed for 24 weeks after surgery. Body weight, food intake and fasting blood glucose level were tested at 0, 1, 3, 6, 12, 24 weeks after the operation in those groups. The concentrations of insulin and glucagon-like peptide-1 (GLP-1) concentrations were measured before (baseline) and then 30, 60, 120, and 180 minutes after OGTT at 0, 12, 24 weeks after the operation.

RESULTSMean operating time of all groups was similar. The mean body weight and food intake decreased significantly at 1 week after surgery (P < 0.01) and with no differences among the groups. Fasting blood glucose level decreased significantly after surgery in all the operation groups through the entire follow-up period (P < 0.05). No significant changes in fasting blood glucose level in SO group was found in 12 weeks after the operation, and it increased at 12 and 24 weeks after. Fasting blood glucose levels in group B decreased significantly compared with group A (P < 0.05), but no difference was found among group B, C and D (P > 0.05). Oral glucose-stimulated peak (30 min) levels of blood insulin and GLP-1 increased markedly in operation groups (A, B, C and D) after surgery (P < 0.01). Compared with group A, peak levels of blood insulin and GLP-1 in group B were strikingly higher (P < 0.05), but no difference was found when compared with group C or D (P > 0.05).

CONCLUSIONSIn spontaneously non-obese type 2 diabetes mellitus rats, small intestinal exclusion including proximal gut is effective in terms of glucose control and has no direct relation with body weight and food intake loss. Restoration of the first-phase insulin secretion and high secretion of GLP-1 in type 2 diabetic subjects after gastrointestinal bypass surgery seem to be helpful to diabetes control. Taking intestinal nutrient absorption into consideration, duodenal-jejunal bypass may be a better surgery for diabetes control.