Glucagon-like peptide-2 and intestinal adaptation: an historical and clinical perspective

Of the many models of intestinal adaptation, the structural and functional changes seen in the residual small bowel following jejunectomy or ileectomy are the most predictable and best studied. There are three major mechanisms for these adaptive phenomena: changes in i) luminal nutrition, ii) pancreatico-biliary secretions and iii) hormonal factors. Observations in a unique patient with an "enteroglucagon"-secreting tumor of the kidney associated with massive small bowel enlargement, provided the strongest evidence, at that time (>30 y ago), in favor of hormonal factors. When the patient's renal tumor was removed, the markedly increased circulating concentrations of the glucagon-like peptide (now presumed to be GLP-2) returned to normal-as did her intestinal anatomy. Subsequent studies showed that there are increased tissue and plasma enteroglucagon (and recently GLP-2) levels in many animal models of intestinal adaptation. This, and anecdotal evidence from three other case reports, coupled with contemporary studies of GLP-2, strongly suggest that this glucagon-like peptide is a potent, but not the sole, enterotrophin.