Exogenous glucagon-like peptide-1 acts in sites supplied by the cranial mesenteric artery to reduce meal size and prolong the intermeal interval in rats

Abstract

Three experiments were done to better assess the gastrointestinal (GI) site(s) of action of GLP-1 on food intake in rats. First, near-spontaneous nocturnal chow meal size (MS), intermeal intervals (IMI) length and satiety ratios (SR = MS/IMI) were measured after infusion of saline, 0.025 or 0.5 nmol/kg GLP-1 into the celiac artery (CA, supplying the stomach and upper duodenum), cranial mesenteric artery (CMA, supplying small and all of the large intestine except the rectum), femoral artery (FA, control) or portal vein (PV, control). Second, infusion of 0.5 nmol/kg GLP-1 was tested after pretreatment with the GLP-1 receptor (GLP-1R) antagonist exendin-4(3–39) via the same routes. Third, the regional distribution of GLP-1R in the rat GI tract was determined using rtPCR. CA, CMA and FA GLP-1 reduced first MS relative to saline, with the CMA route more effective than the others. Only CMA GLP-1 prolonged the IMI. None of the infusions affected second MS or later eating. CA and CMA GLP-1 increased the SR, with the CMA route more effective than the CA route. CMA exendin-4 (3–39) infusion reduced the effect of CMA GLP-1. Finally GLP-1R expression was found throughout the GI tract. The results suggest that exogenous GLP-1 acts in multiple GI sites to reduce feeding under our conditions and that GLP-1R in the area supplied by the CMA, i.e., the small and part of the large intestine, plays the leading role.

Acidosis potentiates endothelium-dependent vasorelaxation and gap junction communication in the superior mesenteric artery

“…The superior mesenteric artery (SMA) plays a vital role in supplying blood to the large part of the gastrointestinal tract (Williams et al, 2016), and plays a direct role in the pathophysiology of the intestinal motility disorders, absorption of nutrients, and blood pressure regulation (Fleming, 2000). It carries more than 10% of the systemic output (Crimi et al, 2012).…”

Cholecystokinin-33, but not cholecystokinin-8 shows gastrointestinal site specificity in regulating feeding behaviors in male rats

“…intra-arterial catheterization of the arteries of the gut, free feeding male rats, measuring eight feeding behaviors and measuring normal rat chow we have shown that the gastrointestinal tract contains sites of action controlling MS and IMI length by CCK-58 (Sayegh et al, 2015; Washington et al, 2016b), gastrin releasing peptide (Washington et al, 2014; Washington et al, 2016a) and glucagon like peptide-1 (Williams et al, 2016). The current study found that in free feeding male rats consuming normal chow the CA and the CMA supply sites of action regulating meal size reduction by CCK-8, whereas only the CMA supplies gastrointestinal sites of action regulating meal size reduction by CCK-33.…”

“…The catheterization procedures have been described in detail in our recent work (Sayegh et al, 2015; Washington et al, 2014; Washington et al, 2016a; Washington et al, 2016b; Williams et al, 2016). All catheters (Micro-Renathane Braintree Scientific R-ITC-SP 9.5) were 9.5" in length.…”

The BB2 receptor antagonist BW2258U89 attenuates the feeding responses evoked by exogenous gastrin releasing peptide-29

“…One catheter was implanted in each rat, and the meal patterns (meal was consumption of ≥ 0.2 g, and intermeal interval [IMI] was no feeding activity for ≥ 15 min), were done as described in details previously (Sayegh et al, 2015; Washington et al, 2014a; Washington et al, 2015; Williams et al, 2016). …”