Abstract

Metabolic surgery is known to impact glucose tolerance but the exact mechanism is still unclear. Based on recently-published data, especially the role of the hindgut may require redefinition. Either a loop duodeno-jejunostomy (DJOS) with exclusion of one third of total intestinal length, a loop duodeno-ileostomy (DiOS, exclusion of two thirds), or SHAM operation was performed in 9-week-old Zucker diabetic fatty rats. One, 3, and 6months after surgery, an oral glucose tolerance test (OGTT) and glucose-stimulated hormone analyses were conducted. Body weight was documented weekly. DJOS and DiOS animals showed significantly better glucose control in all OGTTs than the SHAM group (two-way ANOVA p<0.0001). Body weight developed largely parallel in both intervention groups; SHAM animals had gained significantly less weight after 6months (Mann-Whitney DJOS/DiOS vs. SHAM p<0.05, DJOS vs. DiOS p>0.05). Operative interventions had no impact on GLP-1 and GIP levels at any time point (Mann-Whitney p>0.05 for all). DJOS/DiOS operations could preserve insulin production up to 6months, while there was already a sharp decline of insulin levels in the SHAM group (Mann-Whitney: DJOS/DiOS vs. SHAM p<0.05 for all time points). Additionally, insulin sensitivity was improved significantly 1month postoperative in both intervention groups compared to SHAM (Mann-Whitney DJOS/DiOS vs. SHAM p<0.05). The data of the current study demonstrate a sharp amelioration of glucose control after duodenal exclusion with unchanged levels of GLP-1 and GIP. Direct or delayed hindgut stimulation had no impact on glucose control in our model.

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