Resolution of type 2 diabetes following gastric bypass surgery: involvement of gut-derived glucagon and glucagonotropic signalling?

Certain types of bariatric surgical procedures have proved not only to be effective with regard to treating obesity, but they also seem to be associated with endocrine changes which independently of weight loss give rise to remission of type 2 diabetes. Currently, it is speculated that surgical re-routing of nutrients triggers changes in the release of gastrointestine-derived hormones, which in turn cause amelioration of the diabetic state. The 'hindgut hypothesis' states that surgical re-routing of nutrients to the distal part of the small intestine results in increased secretion and concomitant glucose-lowering effects of glucagon-like peptide-1, whereas the 'foregut hypothesis' emphasises that surgical bypass of the foregut prevents the release of a hitherto unidentified nutrient-induced diabetogenic signal in susceptible individuals. Recent studies have shown that in patients with type 2 diabetes, glucagon is differentially secreted in response to oral and i.v. glucose, respectively, with lack of suppression (and initial net secretion) during oral glucose administration and a perfectly normal suppression during isoglycaemic i.v. glucose administration. These findings could point towards a role for glucagon or gut-derived glucagonotropic signalling as putative diabetogenic signals of the foregut hypothesis. In the present paper the hypotheses describing the glucose-lowering mechanisms of bariatric surgical procedures sharing the common feature of a bypass of the duodenum and the proximal jejunum are outlined and a possible role for glucagon in these is proposed.