Gastric bypass in the pig increases GIP levels and decreases active GLP-1 levels

Publication date: Available online 24 February 2017
Source:Peptides
Author(s): Andreas Lindqvist, Mikael Ekelund, Stefan Pierzynowski, Leif Groop, Jan Hedenbro, Nils Wierup
Gastric bypass surgery results in remission of type 2 diabetes in the majority of patients. The incretin hormones glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) have been implicated in the observed remission. Most knowledge so far has been generated in obese subjects. To isolate the surgical effects of gastric bypass on metabolism and hormone responses from the confounding influence of obesity, T2D or food intake, we performed gastric bypass in lean pigs, using sham-operated and pair-fed pigs as controls. Thus, pigs were subjected to Roux-en-Y gastric bypass (RYGB) or sham-surgery and oral glucose tolerance tests (OGTT). RYGB- and sham-pigs exhibited similar basal and 120-minute glucose levels in response to the OGTT. However, RYGB-pigs had approximately 1.6-fold higher 30-min glucose (p<0.01). Early insulin release (EIR) was enhanced approximately 3.5-fold in the RYGB-pigs (p<0.01). Furthermore, GIP release, both the acute and sustained release (p<0.001 and p<0.01, respectively) were increased approximately 2.5-fold and 1.4-fold, respectively, in RYGB-pigs. While total GLP-1 release increased approximately 2.1-fold after RYGB (p<0.001), active GLP-1 was 33% lower (p<0.01). Interestingly basal DPP4-activity was approximately 3.2-fold higher in RYGB-pigs (p<0.001).In conclusion, RYGB in lean pigs increases the response of GIP, total GLP-1 and insulin, but reduces levels of active GLP-1 in response to an oral glucose load. These data challenge the role of active GLP-1 as a contributor to remission from diabetes after RYGB.



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