Increasing GLP-1 Circulating Levels by Bariatric Surgery or by GLP-1 Receptor Agonists Therapy: Why Are the Clinical Consequences so Different?

Figure 1

Evidence that physiological metabolic actions of GLP-1 are dependent on integrity of vagal nerve. (a) Stimulation of the celiac branch of the subdiaphragmatic vagus nerve (A) significantly stimulated the secretion of GLP-1 [44]. Enhancement of insulin secretion and reduction of glucagon secretion during OGTT by DPP-IV inhibitor or by GLP-1 analogs were reduced in vagotomized subjects (B) [45, 46]. GLP-1 is secreted during meal by the gut and partly reached the portal vein. Chemical destruction of the afferent fibers of the periportal vagus nerve including the hepatoportal sensor (C) limits the effects of portal GLP-1 on glucose metabolism [50]. Administration of physiological doses of GLP-1 into the portal vein modified the electrical activity of vagus nerve fibers [51] and portal perfusion of low doses of an antagonist of GLP-1 caused hyperglycemia during the concomitant oral administration of glucose [52]. (b) In mice denervated at birth by the injection of capsaicin, incretin effect was lost [43]. NTS: nucleus tractus solitarius. Pictures of organs and mice from Servier Medical Art.